Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pons”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources
PubMed1998

Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase.

HDL levels are inversely related to the risk of developing atherosclerosis. In serum, paraoxonase (PON) is associated with HDL, and was shown to inhibit LDL oxidation. Whether PON also protects HDL from oxidation is unknown, and was determined in the present study. In humans, we found serum HDL PON activity and HDL susceptibility to oxidation to be inversely correlated (r2 = 0.77, n = 15). Supplementing human HDL with purified PON inhibited copper-induced HDL oxidation in a concentration-dependent manner. Adding PON to HDL prolonged the oxidation lag phase and reduced HDL peroxide and aldehyde formation by up to 95%. This inhibitory effect was most pronounced when PON was added before oxidation initiation. When purified PON was added to whole serum, essentially all of it became HDL-associated. The PON-enriched HDL was more resistant to copper ion-induced oxidation than was control HDL. Compared with control HDL, HDL from PON-treated serum showed a 66% prolongation in the lag phase of its oxidation, and up to a 40% reduction in peroxide and aldehyde content. In contrast, in the presence of various PON inhibitors, HDL oxidation induced by either copper ions or by a free radical generating system was markedly enhanced. As PON inhibited HDL oxidation, two major functions of HDL were assessed: macrophage cholesterol efflux, and LDL protection from oxidation. Compared with oxidized untreated HDL, oxidized PON-treated HDL caused a 45% increase in cellular cholesterol efflux from J-774 A.1 macrophages. Both HDL-associated PON and purified PON were potent inhibitors of LDL oxidation. Searching for a possible mechanism for PON-induced inhibition of HDL oxidation revealed PON (2 paraoxonase U/ml)-mediated hydrolysis of lipid peroxides (by 19%) and of cholesteryl linoleate hydroperoxides (by 90%) in oxidized HDL. HDL-associated PON, as well as purified PON, were also able to substantially hydrolyze (up to 25%) hydrogen peroxide (H2O2), a major reactive oxygen species produced under oxidative stress during atherogenesis. Finally, we analyzed serum PON activity in the atherosclerotic apolipoprotein E-deficient mice during aging and development of atherosclerotic lesions. With age, serum lipid peroxidation and lesion size increased, whereas serum PON activity decreased. We thus conclude that HDL-associated PON possesses peroxidase-like activity that can contribute to the protective effect of PON against lipoprotein oxidation. The presence of PON in HDL may thus be a major contributor to the antiatherogenicity of this lipoprotein.

Animals↗
PubMed2002

Paraoxonase activities in Minnan and Hakka.

Three phenotypes of paraoxonase (PON) have been found in population studies. The B type gene frequency varies among different populations. The Singaporean Chinese gene frequency is trimodal. The gene frequency of British Chinese populations was neither bimodal nor trimodal. We conducted a study to determine the frequency distribution of PON in the Minnan and Hakka populations. We collected blood samples and questionnaires from Minnan and Hakka subjects from Nantou County, Taiwan, excluding those with PON confounding factors. The blood samples were then examined for PON-non-NaCl (PON without salt stimulation), PON-NaCl (PON with salt stimulation) and arylesterase activities. We compared median differences in age, sex, PON-non-NaCl, PON-NaCl, arylesterase, and PON-NaCl/arylesterase between Minnan and Hakka populations using chi-square and rank analysis of variance (ANOVA), adjusted for age. There were 258 Minnan and 67 Hakka subjects without confounding factors. None of the frequency distributions for PON-non-NaCl, PON-NaCl, or PON-NaCl/arylesterase was clearly bimodal or trimodal. Hakka were older and had increased PON-non-NaCl, PON-NaCl, and PON-NaCl/arylesterase when compared with Minnan, but only age and PON-non-NaCl were significantly different. Hakka and Minnan may have more heterozygous AB phenotype for PON, which might explain why the frequency distribution is not trimodal or bimodal. Marriage among Minnan, Hakka, Aborigines, and other Mainland Chinese in Taiwan may be responsible for difficulty in differentiating gene frequencies among subpopulations by PON phenotype. Nonetheless, the Hakka appeared to have greater PON activity than the Minnan. Subpopulation in itself may be a factor for higher PON activity among the Hakka after controlling for confounding factors.

Adult↗
PubMed2001

[Analysis of regional cerebral blood flow and distribution volume in Machado-Joseph disease by iodine-123I IMP single photon emission computed tomography].

Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia. Its clinical features vary greatly in different generations of the same family. Regional cerebral blood flow (rCBF) and distribution volume (Vd) in the pons, cerebellum, and cerebral cortex were measured in 12 patients with MJD by autoradiography (ARG) and the table look-up (TLU) method of iodine-123 IMP (123I-IMP) single photon emission computed tomography (SPECT). Representative cases were as follows: A 46-year-old woman first experienced gait ataxia at age 38. Computed tomography (CT) and magnetic resonance imaging (MRI) showed no atrophy in the pons or cerebellum, but rCBF measured by the 123I-IMP SPECT ARG method detected hypoperfusion in the pons, and cerebellar vermis and hemisphere. A 76-year-old woman first experienced gait ataxia at age 69. CT and MRI findings showed severe atrophy in the pons, and cerebellar vermis and hemisphere. Moreover, rCBF was decreased in the pons, whereas it was not decreased in the cerebellar vermis and hemisphere. In the pons of patients with MJD, rCBF was markedly decreased regardless of disease severity. Because this SPECT finding for the pons looked like a 'dot', we have called it the 'pontine dot sign'. In the MJD group, rCBF was significantly decreased in the pons (Student's t test, p < 0.01) and cerebellar vermis (p < 0.05). The Vd was also significantly decreased in the pons (p < 0.005) in comparison with that for normal subjects. Pearson's correlation analysis yielded a significant relationship between the rCBF in the pons and age at onset (r = 0.578, p < 0.05). There was a strong correlation between the Vd for the pons and age at onset (r = 0.59, p < 0.05). Pearson's correlation analysis also showed a significant relationship between the Vd in the cerebellar hemispheres and International Cooperative Ataxia Rating Scale (r = 0.644, p < 0.05). The pontine rCBFs in patients with early onset MJD, whose pons was not atrophic, decreased more than did those in patients with late onset MJD, whose pons was severely atrophic. This suggests that the SPECT findings are indicative of underlying neurodegenerative processes that began before the onset of clinical symptoms. Different processes seem to function in atrophy and the rCBF decrease in the pons of patients with MJD. These findings will be proved by the increase of the number of cases of MJD. Until now, there has been no report on rCBF and Vd obtained by 123I-IMP SPECT for patients with MJD identified by gene analysis. Our study shows that SPECT measurement of rCBF and Vd is useful for understanding the pathophysiology of MJD.

Aged↗
PubMed2003

Effect of homocysteinylation on human high-density lipoproteins: a correlation with paraoxonase activity.

We investigated the effect of homocysteine (Hcy)-thiolactone on the activity of the enzyme paraoxonase (PON) associated with human high-density lipoprotein (HDL-PON). HDL were isolated from plasma of normolipidemic subjects. The increase in the levels of sulfhydryl groups (-SH) in HDL incubated with Hcy-thiolactone demonstrates that homocysteinylation of HDL occurs. The increase of -SH groups correlated with the basal values of HDL-PON activity (r = -0.73, P <.001, and r = -0.70, P <.002 using 10 micromol/L and 1 mmol/L Hcy-thiolactone, respectively) suggesting a relationship between the susceptibility of HDL to homocysteinylation and HDL-PON activity. A decrease in the activity of the enzyme HDL-PON was observed in homocysteinylated HDL (Hcy-HDL). The negative correlation established between the basal levels of HDL-PON activity and the percentage decrease of HDL-PON activity (r = -0.76, P <.001, and r = -0.86, P <.001 using 10 micromol/L or 1 mmol/L Hcy-thiolactone, respectively) suggests that subjects with higher HDL-PON activity have a lower decrease in PON activity with respect to subjects with lower HDL-PON activity. The positive correlation established between the percentage decrease of PON activity and the percentage increase of -SH groups in Hcy-HDL (r = 0.80, P <.001, and r = 0.76, P <.001 in HDL incubated in the presence of 10 micromol/L and 1 mmol/L Hcy-thiolactone, respectively) suggests that the modifications of HDL-PON activity are likely related to the compositional changes at the lipoprotein surface of Hcy-HDL. The enzyme PON contributes to the protective role of HDL against the oxidative damage and against toxicity exerted by Hcy involved in the development of atherosclerosis. Therefore the significant decrease of the enzyme activity in HDL incubated with Hcy-thiolactone suggests that homocysteinylation could render HDL less protective against oxidative damage and against toxicity of Hcy-thiolactone.

Adult↗
PubMed2003

Serum paraoxonase: effect of the apolipoprotein composition of HDL and the acute phase response.

Genetic variations of paraoxonase (PON) correlate with HDL cholesterol and apolipoprotein A-I (apoA-I), suggesting antiatherogenic properties. Atherosclerosis occurs naturally in humans and rabbits but not in mice. We compared variations of PON arylesterase activity (PON AEase, phenylacetate substrate) in humans, rabbits, and mice. In humans and rabbits, >95% of PON AEase is HDL associated. In mice, about 30% of PON AEase is lipid poor. In the absence of apoA-I in mice, total PON AEase is reduced and >60% is lipid poor. PON AEase level and distribution is restored in apoA-I-/- mice injected with adenoviruses encoding human apoA-I and in transgenic mice expressing human apoA-I at a steady-state level. Thus, while apoA-I is not required for the HDL association of PON AEase, induced variations in apoA-I correlate with changes in HDL-associated, but not lipid-poor, PON AEase. PON AEase associates only with apoA-I- or apoE-containing HDL but not VLDL. In the absence of both apoA-I and apoE, PON AEase is all-lipid-poor. PON AEase is displaced from HDL by ultracentrifugation and following incubation with serum amyloid A. Variations in the PON distribution between HDL and lipid-poor fractions may have important consequences in its antioxidant activity and in atherogenesis.

Acute-Phase Reaction↗
PubMed2003

Serum paraoxonase levels in pancreatic cancer.

BACKGROUND/AIMS: Serum paraoxonase (PON) is a calcium-dependent esterase that is known to contribute to the antioxidant protection conferred by high-density lipoprotein (HDL) on low-density lipoprotein (LDL) oxidation. Serum PON activity was shown to be reduced in patients with diseases such as myocardial infarction, diabetes mellitus, etc in comparison to healthy subjects. However, the relation of serum PON levels to cancer is still not known. So, we intended to measure serum PON, HDL, LDL and very low-density lipoprotein (VLDL) levels and to investigate the relation of serum PON to plasma lipoproteins in the patients with pancreatic cancer. METHODOLOGY: We measured serum PON, HDL, LDL, and VLDL levels in 20 patients with pancreatic cancer and in 20 age-and gender-matched healthy controls. We investigated the relationship between PON and HDL, PON and LDL, and PON and VLDL. RESULTS: Serum HDL levels were lower in the patients than in controls (40.21 +/- 13.82 mg/dL, and 47.30 +/- 6.65 mg/dL, respectively) (p<0.05). Serum LDL and VLDL levels measured in the patient group were not significantly different from those of the control group. Serum PON levels were lower in the patients than in controls (61.57 +/- 22.44 U/L, and 87.50 +/- 23.39 U/L, respectively) (p<0.005). There was a positive correlation between serum PON and HDL levels (r: 0.69, p<0.05). CONCLUSIONS: We concluded that the patients with pancreatic cancer had low PON and HDL levels compared to healthy controls. The importance of PON as a predictive risk factor for cancer should be assessed in future studies.

Aged↗
PubMed2003

Serum paraoxonase levels in gastric cancer.

BACKGROUND/AIMS: Serum paraoxonase (PON) is a calcium-dependent esterase that is known to contribute to the antioxidant protection conferred by high-density lipoprotein (HDL) on low-density lipoprotein (LDL) oxidation. Serum PON activity was shown to be reduced in patients with diseases such as myocardial infarction, diabetes mellitus, etc in comparison to healthy subjects. However, the relation of serum PON levels to cancer is still not known. So, we intended to measure serum PON, HDL, LDL and very low-density lipoprotein (VLDL) levels and to investigate the relation of serum PON to plasma lipoproteins in the patients with gastric cancer. METHODOLOGY: We measured serum PON, HDL, LDL and VLDL levels in 20 patients with gastric cancer and in 20 age-and gender-matched healthy controls. We investigated the relationship between PON and HDL, PON and LDL, and PON and VLDL. RESULTS: Serum HDL levels were lower in the patients than in controls (33.10 +/- 7.75 mg/dL, and 47.30 +/- 6.65 mg/dL, respectively) (p<0.0001). Serum VLDL levels were lower in the patients than in controls (21.65 +/- 6.92 mg/dL, and 33.10 +/- 6.09 mg/dL, respectively) (p<0.0001). Serum LDL levels measured in the patients were not significantly different from those of the controls. Serum PON levels were lower in the patients than in controls (67.10 +/- 17.92 U/L, and 87.50 +/- 23.39 U/L, respectively) and there was a positive correlation between serum PON and HDL levels (r: 0.52, p<0.05). CONCLUSIONS: We concluded that the patients with gastric cancer had low serum PON, HDL, and VLDL levels compared to healthy controls. The importance of PON as a predictive risk factor for cancer should be assessed in future studies.

Adult↗
PubMed2003

[A follow-up study on brainstem atrophy in progressive supranuclear palsy--when does brain MRI contribute to the differential diagnosis between progressive supranuclear palsy and Parkinson disease?].

OBJECTIVE: To investigate when the MRI can discriminate progressive supranuclear palsy (PSP) from Parkinson disease (PD). METHODS: We obtained the following parameters using T1-weighted axial images of the midbrain and the middle pons from 40 studies of 17 PSP patients and 26 studies of 26 PD patients; 1. anteroposterior diameter of the pons (Pons AP), 2. anteroposterior length of the pontine tegmentum (Pons T), 3. anteroposterior diameter of the midbrain (Midbrain AP), 4. ratio of anteroposterior diameter of the pontine base to that of the pontine tegmentum (Pons B/T ratio), 5. ratio of the sum of the bilateral crus cerebri widths to the midbrain AP (Midbrain [Cr + Cl]/AP ratio). All the PSP patients were studied more than twice and each study was classified into four groups according to the duration of the illness; (1) less than 24 months (7 studies), (2) from 24 to 47 months (10 studies), (3) from 48 to 71 months (14 studies) and (4) 72 months or longer (9 studies). RESULT: The first MRI studies (duration of disease 39.9 +/- 22.1 months) were compared with the second studies (duration of disease 67.6 +/- 31.6 months) in 17 PSP patients. Pons AP, Pons T, and Midbrain AP were significantly smaller in the second studies, indicating progressive pontine and midbrain atrophy. Compared with the PD group, the PSP group showed significant atrophy four years after onset of the disease in Pons AP and two years in Pons T. Pons B/T ratio, and Midbrain [Cr + Cl]/AP ratio were significantly smaller in the PSP group two years after onset, suggesting midbrain and pontine tegmentum atrophy. The diagnostic MRI criteria of Pons B/T ratio more than four and Midbrain [Cr + Cl]/AP ratio more than two each showed accuracy in PSP of more than 70% two years after onset. CONCLUSIONS: Discrimination of PSP from PD was difficult during the first two years after onset. The atrophic process in the midbrain and the pontine tegmentum may precede that of the pontine base. Pons B/T ratio and Midbrain [Cr + Cl]/AP ratio presented here are potentially good indexes for the discrimination of these two diseases.

Aged↗
PubMed1998

Serum paraoxonase activity and its relationship to diabetic complications in patients with non-insulin-dependent diabetes mellitus.

Paraoxonase (PON) is an esterase associated with high-density lipoprotein (HDL). Serum PON activity is affected by PON gene polymorphism (L/M, Leu-Met54, and Q/R, Gln-Arg191). We investigated PON activity and polymorphism in 108 patients (53 men and 55 women) with non-insulin-dependent diabetes mellitus (NIDDM) and 161 control subjects (82 men and 79 women) matched to the patients by age and gender. Serum PON activity was determined using paraoxon as a substrate. PON gene polymorphisms were detected by the restriction fragment length polymorphism method after a polymerase chain reaction. The mean PON activity in the patients was significantly lower than in the controls (116+/-55 and 162+/-57 U/L, respectively, P < .001). The distribution of each genotype showed no difference between the patient and control groups, and PON activity increased in the order of the QQ < OR < RR genotype and MM < LM < LL genotype in both groups. However, among each genotype subgroup, the activity was lower in patients than in controls. Forty-one patients with retinopathy had lower PON activity than those without the complication (94+/-36 and 129+/-61 U/L, respectively, P < .002). There was also a significant difference in PON activity between patients with and without overt proteinuria (93+/-38 and 122+/-58 U/L, respectively, P < .05). Logistic analysis showed that serum PON activity was one of the significant factors for retinopathy. These results suggest that decreased PON activity in patients with NIDDM is involved in diabetic vascular complications.

Adult↗
PubMed2002

Relationship of paraoxonase and serum lipids in Taiwan.

Paraoxonase (PON) is structurally associated with the high-density lipoprotein fraction of serum, suggesting a role for this enzyme in lipoprotein metabolism. In Chinese Singaporeans, triglycerides (TG) had significant positive correlation with PON but high-density lipoprotein cholesterol (HDL-C) did not. Our paper investigates the influence of PON on serum lipids under controlling confounding factors in Taiwanese. Blood samples and questionnaires were collected from 476 Taiwanese with no participant excluded for any reason. Cases were examined for biochemistry, PON, TG, cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and HDL-C. PON phenotypes were determined by Hardy-Weinberg equilibrium. We compared median differences in PON, TG, TC, HDL-C and LDL-C between genders by means of the Wilcoxon Rank Sums test. Relationships among PON, TG, TC, HDL-C and LDL-C were represented by Pearson's correlation. A rank multiple regression analysis was also used to analyze the association between PON, TG, TC, HDL-C and LDL-C adjusted for age, gender and diabetes mellitus, since no uremia, acute myocardial infarction or peripheral neuropathy was present in our cases. Median TG and LDL-C were higher in males than in females, but median HDL-C was higher in females. For women and the total group, TC and HDL-C showed a significant positive correlation with PON. Only HDL-C showed a positive correlation with PON adjusted for age, gender and diabetes mellitus. PON is influenced by many confounding factors. Only after adjusting for the confounding factors in this study, HDL-C is positively correlated to PON like the structural relationship.

Aryldialkylphosphatase↗
PubMedDate not supplied

Paraoxonase 55 and 192 polymorphism and its relationship to serum paraoxonase activity and serum lipids in Turkish patients with non-insulin dependent diabetes mellitus.

We investigated the effect of PON 55 and PON 192 polymorphisms on serum PON1 activity and lipid profiles in 213 non-insulin dependent diabetes mellitus (NIDDM) individuals and 116 non-diabetic controls among Turkish subjects. The distribution of PON 55/192 gene polymorphism was determined by polymerase chain reaction-based restriction fragment length polymorphism. Serum lipid levels were measured enzymically. PON activity was measured by spectrophotometric assay of p-nitrophenol production following addition of paraoxon. We found that PON 55 and 192 genotype distribution was similar in patients and controls and paraoxonase activity was generally lower in diabetics than in control subjects. We showed that PON 55 and 192 genotypes have a major effect on serum PON activity. PON 192 BB homozygotes had significantly higher PON activity than AA and AB genotypes among the control and NIDDM populations (p<0.001). PON 55 MM homozygotes had significantly lower PON activity than did LL and LM genotypes in control and NIDDM populations (p<0.05). The PON1 55 and 192 polymorphisms did not consistently influence the serum lipid profiles in either population. In conclusion, our results suggest that the paraoxonase activities are affected by PON1 genetic variability in Turkish NIDDM patients and controls.

Aryldialkylphosphatase↗
PubMed2003

Light, but not heavy alcohol drinking, stimulates paraoxonase by upregulating liver mRNA in rats and humans.

Paraoxonase 1 (PON) may contribute to the cardioprotective action of high-density lipoprotein (HDL) because it inhibits low-density lipoprotein (LDL) oxidation, a prerequisite for the onset of atherosclerosis. Because light drinking and heavy drinking have diametrically opposite effects on cardioprotection, we have determined the effects of ethanol dosage on rat serum PON activity and its hepatic expression. Furthermore, we have investigated PON activity and polymorphism in human light and heavy drinkers. Our results confirm that HDL-PON inhibited LDL oxidation, destroyed oxidized LDL, and inhibited its uptake by macrophages. Light ethanol feeding caused a 20% to 25% (P <.05) increase in PON activity in both serum and liver and a 59% (P <.001) increase in the level of liver PON mRNA compared with pair-fed control rats. In contrast, heavy ethanol feeding caused a 25% (P <.05) decrease in serum and liver PON activities with a 51% (P <.01) decrease in liver PON mRNA level. Light drinkers had a 395% (P <.001) higher, whereas heavy drinkers had a 45% (P <.001) lower serum PON activity compared with nondrinkers. Significantly, the number of homozygotes versus heterozygotes with respect to high or low activity PON phenotype was similar in all the groups. Therefore, we conclude that light drinking upregulates, whereas heavy drinking downregulates PON activity and its expression, irrespective of its genetic polymorphism.

Adult↗
PubMed2001

Cysteine substitutions in apolipoprotein A-I primary structure modulate paraoxonase activity.

Paraoxonase (PON) is transported primarily on apolipoprotein A-I (apoA-I) -containing high-density lipoprotein (HDL) and is thought to protect against early atherogenic events including low-density lipoprotein (LDL) oxidation and monocyte migration. It has been proposed that apoA-I may be necessary for PON's association with plasma HDL. On the basis of this, we examined the effect of apoA-I on PON's enzymatic activity and its ability to associate with HDL. Additionally, we examined whether changes in apoA-I primary structure (cysteine substitution mutations) could modulate these effects. Chinese hamster ovary cells stably transfected with human PON1A cDNA were incubated in the presence and absence of recombinant wild-type apoA-I (apoA-I(WT)) and specific Cys substitution mutations. Extracellular accumulation of PON activity in the presence of apoA-I(WT) was 0.095 +/- 0.013 unit/mg of cell protein (n = 7) compared to 0.034 +/- 0.010 unit/mg of cell protein in the absence of apoA-I (n = 7), a 2.79-fold increase in activity when apoA-I was incubated with the cells. Lipid-free apoA-I did not increase PON activity, while preformed nascent HDL increased PON activity only 30%, suggesting that maximal PON activity is lipid-dependent and requires coassembly of PON and apoA-I on nascent HDL. The cysteine mutations R10C, R27C, and R61C significantly increased (p < 0.01) PON activity 32.6% +/- 14.7%, 31.6% +/- 18.9%, and 27.4% +/- 20%, respectively, over that of wild type (WT). No changes in PON activity were observed with apoA-I cysteine substitution mutations in the C-terminal portion of the protein. The data suggest that, for optimal PON activity, coassembly of the enzyme onto nascent HDL is required and that the N-terminal region of apoA-I may be important in the assembly process.

Amino Acid Substitution↗
PubMed2004

Protective effect of paraoxonase activity in high-density lipoproteins against erythrocyte membranes peroxidation: a comparison between healthy subjects and type 1 diabetic patients.

High-density lipoproteins (HDL) plays a key role in the protection against oxidative damage of lipoprotein and biological membranes. The aim of the present study was to investigate the relationship between the antioxidant role of HDL and the HDL-paraoxonase (PON) activity in healthy subjects and in type 1 diabetic patients. Moreover, the ability of HDL of controls and diabetic patients to protect and/or repair biological membranes from oxidative damage was studied. HDL were isolated from 31 type 1 diabetic patients and 31 sex- and age-matched healthy subjects and immediately used to evaluate lipid hydroperoxides and HDL-PON activity. Erythrocyte membranes obtained from healthy subjects were oxidized with 2,2-azo-bis(2-aminidinopropane)dihydrochloride and then incubated in the presence of HDL isolated from healthy or type 1 diabetic subjects, with measurements of membrane lipid hydroperoxides before and after the incubation. HDL from type 1 diabetic patients showed higher levels of lipid hydroperoxides and a lower activity of HDL-PON than healthy subjects. Moreover, HDL of type 1 diabetic patients protected less efficiently erythrocyte membranes against oxidative damage compared with HDL from healthy subjects. A negative correlation was found between HDL-PON activity and the levels of hydroperoxides of HDL, confirming the relationship between PON and lipid peroxidation and suggesting that subjects with low PON activity are more exposed to oxidative damage than subjects with high PON activity. The ability of HDL to protect erythrocyte membranes was positively correlated with HDL-PON activity and negatively correlated with the levels of lipid hydroperoxides of HDL of healthy subjects. These results confirm a linkage between PON activity and lipid peroxidation of lipoproteins and suggest that the ability of HDL to protect erythrocyte membranes might be related to the PON activity. It might be hypothesized that the decrease of PON activity in diabetic patients and the lower HDL protective action against membrane peroxidation could contribute to acceleration of arteriosclerosis in type 1 diabetes mellitus.

Adult↗
PubMed1995

Comparison of purified human and rabbit serum paraoxonases.

Rabbit serum paraoxonase (PON) activity was reported to be nearly 20 times greater than that found for humans and all other mammalian species tested, to date. However, 85% of the amino acid residues are identical in human and rabbit PONs, and the two purified PONs show similar substrate specificity patterns. Both are stimulated by phospholipids and have two asparagine-linked sugar chains. Both also have one intramolecular disulfide bond and one free sulfhydryl residue per molecule. Both require Ca2+ for stability and for catalytic activity. Zn2+ and Cd2+ also stabilize both PONs and prevent irreversible denaturation, but neither metal confers catalytic activity. Maximum specific activities for both esterases were approximately 2,000 units of arylesterase activity/mg protein. In contrast, rabbit PON is more stable than human PON to heat inactivation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis treatment. Chelex 100 strips Ca2+ from human PON more easily, and EDTA is less inhibitory with rabbit PON. We conclude that human and rabbit PONs have very similar active centers, but the latter binds Ca2+ more tightly, is a more stable enzyme, and is maintained at 3- to 4-fold higher steady-state concentrations in serum than its human counterpart. PON activity depends on adequate Ca2+ being available; therefore, apparently much higher levels of PON activity in rabbits can be explained by the reduced Ca2+ concentrations present in the early assay methods.

Amino Acid Sequence↗
PubMed1998

[Relationship between water content and magnetization transfer ratio in the rat brain using a new cardiac perfusion model with different osmotic gradients].

We devised a method to make a gradient water content model of the rat brain by perfusing osmotic NaCl solution from the left ventricule. Using this model we measured the water content and magnetization transfer ratio (MTR) of the frontal lobe and the pons as examples of gray and white matter, respectively. When we perfused five levels of osmotic NaCl solution (0, 0.9, 1.8, 3.6 and 7.2%) to respective groups of four rats, mean water content decreased from 81.5% at 0% to 75.9% at 7.2% NaCl in the frontal lobe and from 74.1% to 61.0% in the pons, while MTR increased from 21.5% to 24.2% in the frontal lobe and from 22.9% to 27.3% in the pons. Thus water content was significantly higher (p < 0.01) in the frontal lobe than the pons at each level of NaCl concentration, and MTR was significantly higher in the pons than the frontal lobe (p < 0.05 approximately 0.01, except at 0%). Further, the grade of alteration was higher in the pons than the frontal lobe for both water content and MTR. Excellent correlations between MTR and water content were observed with coefficients of -0.75 and -0.82 for the frontal lobe and pons, respectively, and the regression lines showed higher position and slope in the frontal lobe than the pons. From these results we concluded that the pons is rich in free water of extracellular fluid that moves easily between the myelin sheath, whereas in the frontal lobe, water is so diffusely mingled with membranes and favorable to bound water that the magnetization transfer effect is more effective, yielding a higher MTR for the same water content and showing greater change in MTR for the same change in water content as the pons.

Animals↗
PubMed2001

High salt intake and the brain renin--angiotensin system in Dahl salt-sensitive rats.

OBJECTIVES: To assess changes in the activity of the brain renin-angiotensin system during (i) the development of salt-sensitive hypertension; and (ii) the prevention of salt-sensitive hypertension by blocking brain 'ouabain'. METHODS: In protocol I, angiotensin converting enzyme (ACE) mRNA and activity and angiotensin I and II levels were assessed in the hypothalamus and pons of Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats on regular (120 micromol Na+ per g) or high (1370 micromol Na+ per g) salt diet from 4-6 weeks or 4-9 weeks of age. In protocol II, ACE mRNA and activity were assessed in the hypothalamus and pons in Dahl S on regular or high salt treated with intracerebroventricular (i.c.v.) Fab fragments blocking brain 'ouabain' or gamma-globulins, and in Dahl R on high or regular salt ACE mRNA was assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay and angiotensin I and II by radioimmunoassay after high-performance liquid chromatography. In protocol III, effects of i.c.v. angiotensin I and i.c.v. bradykinin on renal sympathetic nerve activity (RSNA), heart rate and blood pressure before and after i.c.v. captopril were assessed in Dahl S and R rats on regular or high salt intake from 4-8 weeks of age. RESULTS: High salt diet caused a gradual, but marked increase in blood pressure in Dahl S but not Dahl R rats. Dahl S rats showed small but significant increases in ACE mRNA in the hypothalamus on regular salt diet. In Dahl S rats on high salt diet for 2 or 5 weeks ACE mRNA levels significantly increased in both hypothalamus and pons, compared with Dahl R rats on either diet or Dahl S rats on regular diet. After 5 weeks of high salt diet, ACE mRNA levels in the hypothalamus in Dahl S rats were almost three-fold higher and in the pons two-fold higher than in Dahl R rats on either diet or Dahl S on regular salt diet. High salt diet also increased ACE activity of the hypothalamus and pons in Dahl S but not Dahl R. Consistent with this increased ACE activity, central responses to angiotensin I were clearly enhanced and to bradykinin markedly diminished in Dahl S on high salt intake. Chronic blockade of brain 'ouabain' by i.c.v. Fab fragments prevented the increases in blood pressure, ACE mRNA and activity in the hypothalamus and pons by high salt intake in Dahl S rats. Angiotensin I levels in the hypothalamus and pons were similar in both groups of rats and there were no significant changes caused by high salt diet in Dahl S and R rats. On regular salt intake angiotensin II levels in the hypothalamus of Dahl S rats showed a significant decrease as compared with Dahl R rats on regular salt diet, and were similar in the pons of the two strains. High salt intake did not affect angiotensin II levels in either hypothalamus or pons in Dahl S and R rats. CONCLUSIONS: These results indicate that high salt intake increases blood pressure, ACE expression and activity in the hypothalamus and pons of Dahl S rats without a parallel increase in angiotensin II levels. Effects of high salt intake on ACE mRNA and activity appear to be secondary to activation of brain 'ouabain'.

Angiotensin I↗
PubMed1995

A polymorphism of the paraoxonase gene associated with variation in plasma lipoproteins in a genetic isolate.

The Hutterite Brethren are a genetic isolate characterized by high indices of relatedness and a communal agrarian lifestyle. We hypothesized that variation of the paraoxonase (PON) gene that underlies the interindividual variation in plasma PON activity would be associated with variation in fasting plasma lipoprotein variables in this group. In 793 Hutterites, we measured plasma lipids, lipoproteins, and apolipoproteins and analyzed DNA for genotypes of the protein polymorphism at amino acid residue 192 of PON. We observed that genotypes of PON were significantly associated with variation in plasma concentrations of total, HDL, non-HDL, and LDL cholesterol, total triglycerides, and apolipoprotein (apo) B. Homozygotes for the low-activity variant of PON had significantly lower levels of plasma apoB-related biochemical variables than heterozygotes and homozygotes for the high-activity variant of PON. Homozygotes for the low-activity variant of PON also had significantly lower ratios of total cholesterol/HDL cholesterol, LDL cholesterol/HDL cholesterol, and apoB/apoA-I than heterozygotes and homozygotes for the high-activity variant of PON. We found no evidence for a gene-gender interaction for any plasma lipoprotein variable. The PON polymorphism accounted for about 1% of the variation in total cholesterol and related lipoprotein traits in the Hutterites. These observations suggest that PON is a significant genetic determinant of plasma lipoprotein levels.

Adult↗