Biomedical subjects

N Taniguchi

Publications and source records attributed to N Taniguchi.

At least 199 records · Page 11Linked to original sources

PubMed1997

Gene transfection-mediated overexpression of beta1,4-N-acetylglucosamine bisecting oligosaccharides in glioma cell line U373 MG inhibits epidermal growth factor receptor function.

N-linked oligosaccharides appear to be important for the function of the epidermal growth factor (EGF) receptor. In a previous study (Rebbaa, A., Yamamoto, H., Moskal, J. R., and Bremer, E. G. (1996) J. Neurochem. 67, 2265-2272), we showed that binding of the erythroagglutinating phytohemagglutin lectin from Phaseolus vulgaris to the bisecting structures on the EGF receptor from U373 MG glioma cells blocked EGF binding and receptor autophosphorylation. In this study we examined the consequences of overexpression of the bisecting structure on the EGF receptor by gene transfection of U373 MG cells with the N-acetylglucosaminyltransferase III (GnT-III). This modification leads to a significant decrease in EGF binding and EGF receptor autophosphorylation. In addition, the cellular response to EGF was found to be altered. Proliferation of U373 MG cells in serum-free medium is inhibited by EGF. In contrast, proliferation of the GnT-III-transfected cells was stimulated by EGF. These data demonstrate that changes in EGF receptor glycosylation by GnT-III transfection reduces the number of the active receptors in U373 MG cells and that this change results in change in the cellular response to EGF.

Acetylglucosamine↗

PubMed1997

Involvement of reactive oxygen intermediates in spontaneous and CD95 (Fas/APO-1)-mediated apoptosis of neutrophils.

Apoptosis is well known to be mediated by oxidative stress. To evaluate the functional role of reactive oxygen intermediates (ROI) produced by neutrophils, we compared the rates of apoptosis in neutrophils isolated from normal donors and from patients with chronic granulomatous disease (CGD), a hereditary defect in ROI production. Spontaneous cell death in CGD neutrophils in vitro was significantly inhibited relative to normal neutrophils. The acceleration of apoptosis induced by anti-Fas monoclonal antibody (MoAb) in CGD neutrophils was much slower than that seen in normal neutrophils. These findings suggest that the apoptosis of neutrophils may be mediated by endogenous oxidative products. This suggestion was confirmed by observation that apoptosis of normal neutrophils was markedly inhibited by reduction of intracellular levels of hydrogen peroxide (H2O2). The inhibition of apoptosis in normal neutrophils by adding catalase occurred regardless of the presence of anti-Fas MoAb. H2O2 increased both spontaneous apoptosis and Fas-mediated apoptosis of the CGD neutrophils in proportion to that seen in normal neutrophils. Although several factors that mediate the apoptosis of neutrophils remain to be determined, these results suggest that ROI are major mediators of the apoptosis in neutrophils and may be involved in Fas-mediated signal transduction pathway.

Apoptosis↗

PubMed1997

Bisecting GlcNAc structures act as negative sorting signals for cell surface glycoproteins in forskolin-treated rat hepatoma cells.

The bisecting N-acetylglucosamine residue is formed by UDP-N-acetylglucosamine:beta-D-mannoside-beta-1, 4-N-acetylglucosaminyltransferase III (GnT-III), a key branching enzyme for N-glycans. We found that forskolin, an adenylyl cyclase activator, markedly enhanced GnT-III at the transcriptional level in various hepatoma cells and hepatocytes, resulting in an increase of bisecting GlcNAc residues in various glycoproteins, as judged from the lectin binding to erythroagglutinating phytohemagglutinin (E-PHA). In whole cell lysates, the E-PHA binding was increased, and leukoagglutinating phytohemagglutinin (L-PHA) binding was decreased at 12 h after forskolin treatment, by time, both GnT-III activity and mRNA had reached the maximum levels. In contrast, the binding capacity as to E-PHA, determined by fluorescence-activated cell sorting on the cell surface, was decreased, suggesting that bisecting GlcNAc structures in certain glycoproteins changed the expression levels of glycoproteins and decreased their sorting on the cell surface. Fractionated organelles of M31 cells showed that the binding capacity as to E-PHA was mainly localized in Golgi membranes and lysosomes. This was also supported by a fluorescence microscopy. In order to determine whether or not the bisecting GlcNAc residue acts as a sorting signal for glycoproteins, N-oligosaccharide structures of lysosomal-associated membrane glycoprotein 1 and beta-glucuronidase, gamma-glutamyltranspeptidase, and secretory glycoproteins such as ceruloplasmin and alpha-fetoprotein were measured by E-PHA and L-PHA blotting after immunoprecipitation. The expression levels of lysosomal membrane glycoprotein 1 and gamma-glutamyltranspeptidase on the cell surface were decreased at 12 h after forskolin treatment, indicating that the bisecting GlcNAc structure may act as a negative sorting signal for the cell surface glycoproteins and may alter the characteristics of hepatoma cells. This is the first report on glycoprotein sorting related to a specific structure of oligosaccharides, bisecting GlcNAc.

Acetylglucosamine↗

PubMed1997

Possible role of coexpression of CD9 with membrane-anchored heparin-binding EGF-like growth factor and amphiregulin in cultured human keratinocyte growth.

CD9 is a protein with 4 transmembrane domains, and functions as a cell surface antigen. We have previously reported that CD9 functions as an up-regulator of membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) activity, which is a potent mitogen as well as a soluble HB-EGF. Anti-CD9 antibodies can neutralize the juxtacrine activity of proHB-EGF when both CD9 and proHB-EGF are coexpressed. We demonstrated here: (1) the CD9 gene was transcribed and translated in the cultured human keratinocytes; (2) anti-CD9 antibody inhibited the approximately 50% growth of human keratinocytes in culture; (3) CD9 was coprecipitated with proHB-EGF and membrane-anchored amphiregulin (proAR), and (4) the transient coexpression of CD9 with proHB-EGF or proAR in mouse L cells up-regulated their juxtacrine growth factor activities. These results suggest that CD9 would make a heterodimer and/or trimer complex with proHB-EGF and proAR, and might cooperate with proHB-EGF and proAR for human keratinocyte growth in a juxtacrine manner.

Amphiregulin↗

PubMed1997

Heat shock-induced manganese superoxide dismutase enhances the tolerance of cardiac myocytes to hypoxia-reoxygenation injury.

We evaluated the mechanism of the heat shock-induced tolerance to ischemia-reperfusion using a model of hypoxia-reoxygenation tolerance in neonatal rat cardiac myocytes. Myocytes exposed to heat shock (42 degrees C, 1 h) exhibited a 1.8-fold increase in levels of manganese superoxide dismutase (Mn-SOD) mRNA after 40 min v control cells. The concentration of Mn-SOD increased from 0.49+/-0.04 microg/mg protein to 0.68+/-0.05 microg/mg protein after 24 h (P<0. 05). Levels of heat shock protein 72 (hsp72; inducible form) mRNA and protein also increased markedly after heat shock exposure. The release of creatine kinase (CK) from the myocytes and the depletion of ATP level in the myocytes exposed to hypoxia (pO2: 7 mmHg, 3 h) and reoxygenation (pO2: 143 mmHg) were significantly reduced following heat shock pretreatment (CK: 1.18+/-0.14 U/l v 0.62+/-0.13 U/l, ATP: 11.9+/-1.1 nmol/mg protein v 16.2+/-1.0 nmol/mg protein, P<0.05). Treatment with antisense oligodeoxyribonucleotides to Mn-SOD (1.5 micromol/l) completely inhibited the heat shock-associated induction of Mn-SOD (0.47+/-0.05 microg/mg protein), but not hsp72, and abolished the heat shock-induced decrease in CK release (1.04+/-0.15 U/l, P<0.05) and depletion of ATP level (11. 2+/-1.1 nmol/mg protein, P<0.05). Results indicate that Mn-SOD induction, not hsp72 induction, plays a pivotal role in the heat shock-induced acquisition of tolerance to hypoxia-reoxygenation in neonatal rat cardiac myocytes.

Animals↗

PubMed1997

Identification of alpha 1-adrenoceptor subtypes in the human prostatic urethra.

To identify the alpha 1-adrenoceptor subtypes in the human prostatic urethra, we compared the potencies of various alpha 1-adrenoceptor agonists and antagonists in inhibiting [3H]tamsulosin binding to human prostatic urethral membranes with their potencies in inhibiting the binding of (+)-beta-([125I]iodo-4-hydroxyphenyl)ethylaminomethyl-tetralone ([125I]HEAT) to cloned human alpha 1a, alpha 1b and alpha 1d subtypes. The alpha 1A-selective antagonists 5-methylurapidil and (+)niguldipine showed higher affinities for both cloned alpha 1a and urethral alpha 1-adrenoceptors than for cloned alpha 1b- and alpha 1d-adrenoceptors. NS-49, (R)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide hydrochloride, recently characterized as an alpha 1A-selective agonist, also showed high affinity for the cloned alpha 1a subtype and urethral alpha 1-adrenoceptors. Prazosin showed lower affinity for alpha 1-adrenoceptors in the human prostatic urethra than for any of the three cloned alpha 1-adrenoceptors. Comparison of the affinities of alpha 1-adrenoceptor agonists and antagonists for human prostatic urethral alpha 1-adrenoceptors to their affinities for the three cloned alpha 1 subtypes indicated a close correlation between the affinities for human urethral alpha 1 and the cloned alpha 1a-adrenoceptors. However, prazosin did not conform to this pattern. These findings suggest that the predominant alpha 1-adrenoceptor in the human urethra is the alpha 1A subtype, and that an alpha 1L subtype which has been characterised by its low affinity for prazosin, may also be present.

Adrenergic alpha-Agonists↗

PubMed1997

Hyaluronic acid of wound fluid in adult and fetal rabbits.

Fetal wound healing proceeds without fibrosis or scar formation in contrast to adult wound healing. The mechanisms responsible for this remarkable process are mediated in part through a fetal wound extracellular matrix rich in hyaluronic acid (HA). Polyvinylalcohol sponge (PVA) wound implants were placed pervertebrally at 24 days' gestation in fetal (N = 118) rabbits and in adult (N = 44) rabbits, and then harvested at 1, 2, 3, 4, 5, and 7 days postwounding. To analyze the fetal and adult wound matrix, the HA concentration of wound fluid within the PVA sponge was quantitated using a newly developed assay. A significantly increased (P < .05) HA deposition on days 1 through 7 in the fetal wounds was found compared with the adult wound. These observations may suggest an important physiologic role in fetal wound healing by providing a more fluid and malleable matrix. These results, coupled with earlier findings of the lack of an acute inflammatory response in the fetus, further support the hypothesis that fetal response to injury is significantly different from adult response in this prescience of an implanted PVA sponge.

Aging↗

PubMed1997

Evaluation of the role of lactate dehydrogenase in oxalate synthesis.

The kinetic properties of lactate dehydrogenase (LDH) (EC 1.1.1.27) from spinach leaves were studied in order to evaluate the possible roles of LDH in the production of oxalate. LDH was purified by affinity chromatography on affigel blue and oxamate agarose columns. The pH optimum for the reduction of pyruvate was 7.25, while that for the reduction of glyoxylate was 7. The rate of reduction of pyruvate and glyoxylate at the optimum pH indicated substrate inhibition at concentrations above 8 and 40 mM, respectively. The maximum activity of LDH with pyruvate was about three times greater than with glyoxylate. The pH optimum for the oxidation of lactate was 9, with very low activity below pH 8. Substrate inhibition was apparent at lactate concentrations above 10 mM. LDH was inactive with glyoxylate in the oxidative reaction, which would lead to the biosynthesis of oxalate.

Catalysis↗

PubMed1997

Anticholinergic and calcium antagonistic activities of NS-21 contribute to the inhibition of rat urinary bladder contractions.

1. Pharmacological characteristics of NS-21 and its main metabolite, RCC-36, in the inhibition of rat urinary bladder contractions were investigated both in vitro and in vivo. 2. NS-21 and RCC-36 inhibited muscarinic receptor bindings to rat bladder membranes with [3H]3-quinuclidinyl bezilate (pKi 6.19 and 7.24, respectively), whereas they failed to inhibit the following receptor bindings: adrenergic (alpha 1, alpha 2 and beta), dopaminergic (D1 and D2), adenosine (A1 and A2), histaminergic (H1) and opioid (mu, delta and kappa) receptors. 3. NS-21 and RCC-36 suppressed carbachol-induced contractions of isolated rat detrusor strips in competitive (pA2 6.80 and 7.93, respectively) and noncompetitive (pD'2 5.93 and 5.77, respectively) manners. 4. NS-21 and RCC-36 inhibited CaCl2-induced contractions of rat detrusor strips in the presence of 100 mM K+ (pIC50 6.54 and 5.76, respectively), as well as the 100 mM K(+)-induced 45Ca influx into the isolated bladder strips at > or = 1 microM. 5. Electrical stimulation of the peripheral end of the pelvic nerve in anesthetized rats induced bladder contractions composed of two phases: an initial phasic contraction that was weakly suppressed by atropine, and a tonic contraction that was strongly suppressed by atropine. NS-21 suppressed both contractions to the same degree (ID50 2.65 and 2.19 mg/kg, i.v., respectively). RCC-36 suppressed the tonic contraction (ID50 1.20 mg/kg, i.v.) more markedly than the initial contraction (ID50 7.43 mg/kg, i.v.). 6. These results suggest that NS-21 and RCC-36 suppressed bladder contractions owing to their anticholinergic and calcium antagonistic activities.

Animals↗

PubMed1997

TGF-beta1 triggers oxidative modifications and enhances apoptosis in HIT cells through accumulation of reactive oxygen species by suppression of catalase and glutathione peroxidase.

Transforming growth factor-beta1 (TGF-beta1) is a multifunctional polypeptide that is related to the progression of chronic pancreatitis. However, the mechanism of beta-cell damage by TGF-beta1 is unknown. Treatment with TGF-beta1 enhanced internucleosomal DNA cleavage caused by exogenous hydrogen peroxide in a hamster pancreatic beta-cell line (HIT). TGF-beta1 also induced protein oxidation, assessed by measuring carbonyl groups in proteins, and was involved in reactions that lead to lipid peroxidation. This eventually destructs membrane lipids and forms malondialdehyde. We have investigated its effects on two major antioxidative enzymes, catalase and glutathione peroxidase (GPx). TGF-beta1 suppressed mRNA expression as well as reduced the activities of catalase and GPx. The decrease in the catalase and GPx activities in TGF-beta1-treated cells resulted in an increase in intracellular peroxides as judged by flow cytometric analysis using a peroxide-sensitive dye, 2',7'-dichlorofluorescin diacetate. These data suggest that the augmented production of reactive oxygen species by TGF-beta1 through suppression of antioxidative enzymes may cause cellular damage and consequent apoptosis and induce pancreatitis or diabetes.

Adenoma, Islet Cell↗

PubMed1997

Distribution of heparin-binding EGF-like growth factor protein and mRNA in the normal rat kidneys.

Heparin-binding EGF-like growth factor (HB-EGF), a newly discovered potent mitogen and chemoattractant for smooth muscle cells, is a member of the EGF superfamily and binds to EGF receptors. To investigate the role of HB-EGF in the kidney, we determined the distribution of HB-EGF immunohistochemically in normal rat kidneys. The localization of mRNA expression was also studied by in situ hybridization, using a synthesized digoxigenin-labeled anti-sense riboprobe of HB-EGF. Immunohistochemical and in situ hybridization studies revealed that the tubular epithelial cells of the S3 segment of the outer stripe in the outer medulla were the predominant renal source of HB-EGF. In addition, in the immunohistochemical analysis, HB-EGF was ubiquitously present in the epithelial cells of the proximal tubules and the arterial smooth muscle cells, while HB-EGF expression was not detected in other parts of the kidney, including the glomeruli. Although EGF receptors were found to be present in the proximal tubules as well as in the distal tubules and collecting ducts, EGF has not been found to be expressed in the proximal tubules. Therefore, the present results indicate that HB-EGF might be a ligand for EGF receptors in the proximal tubules and might play a role in the functions of proximal tubules.

Animals↗

PubMed1997

The effect of nitric oxide synthase inhibitor on form-deprivation myopia.

PURPOSE: Form-deprivation myopia (FDM) is believed to result principally from actions of substances that modulate information processing in the retina. We used a chick model to investigate what role nitric oxide (NO), a gaseous neuromodulator, might play in the development of FDM. METHODS: We injected different concentrations of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) (30 ml) into the left eyes and the same volume of saline into the right eyes of 6-day-old chicks. Both eyes of most chicks were occluded for 6 days with translucent goggles. After removal of the goggles, the refraction was measured by retinoscopy and the axial lengths with an A-mode ultrasound. In some chicks we measured the concentration of NOx (nitrite and nitrate) in the retina. A few chicks, not wearing occluders after injection of L-NAME and saline, ERG and refraction, were examined 6 days after the treatment. RESULTS: In chicks that wore occluders, refractive error and axial length were significantly less affected in eyes injected with L-NAME (180, 360, or 540 mM) compared to control (right) eyes. ERG changes were reversible, except in eyes injected with the highest concentration (540 mM) of L-NAME. The eyes of chicks, injected with L-NAME and reared without occlusion, had normal refractive values. After 6 days of form deprivation, the concentration of NOx in the retina of eyes injected with L-NAME (180 mM) was significantly less than the concentration in eyes injected with saline. CONCLUSIONS: The injection of L-NAME before occlusion of developing chick eyes leads to reversible modifications in retinal function and inhibits the development of form-deprivation myopia.

Animals↗

PubMed1997

N-glycosylation is requisite for the enzyme activity and Golgi retention of N-acetylglucosaminyltransferase III.

UDP-N-acetylglucosamine: beta-D-mannoside beta-1,4N-acetylglucosaminyltransferase III (GnT-III, EC 2.4.1.144) is a glycoprotein involved in the biosynthesis of N-linked oligosaccharides. Rat GnT-III contains three potential N-glycosylation sites, which have been predicted to be Asn243, Asn261, and Asn399. To study the roles of N-glycosylation in the GnT-III function, rat GnT-III was expressed in COS-1 cells under tunicamycin or castanospermine treatment. The tunicamycin-treated GnT-III, which was not N-glycosylated, had almost no activity. The castanospermine-treated GnT-III was not localized in the Golgi, but glucosylation did not affect its activity. To clarify the role of individual N-glycosylations, we obtained a series of mutant cDNAs in which some or all of the potential glycosylation sites were eliminated by site-directed mutagenesis, and expressed them in COS-1 cells. All the mutants exhibited lower enzyme activity than the wild-type, but deglycosylation at individual sites had different effects on the enzyme activity. The deglycosylation at Asn243 or Asn261 was more effective on the activity than that at Asn399. The enzyme activity decreased as the number of glycosylation sites decreased. The null glycosylation mutant had no activity, corresponding to the case of tunicamycin-treated wild-type GnT-III. Kinetic analysis revealed that the deglycosylation at Asn243 or Asn261 resulted in slightly lower affinity for the donor substrate, but the other mutation did not significantly change the K(m) value for either the donor or acceptor. None of the mutant GnT-IIIs showed perinuclear localization or Golgi retention, that was observed for the wild-type protein. This is the first demonstration that the glycosyltransferase localized in the Golgi apparatus requires N-glycosylation for its activity and retention.

Animals↗

PubMed1997

Purification and cDNA cloning of GDP-L-Fuc:N-acetyl-beta-D-glucosaminide:alpha1-6 fucosyltransferase (alpha1-6 FucT) from human gastric cancer MKN45 cells.

GDP-L-Fuc:N-acetyl-beta-D-glucosaminide:alpha1-6 fucosyltransferase (alpha1-6 FucT), which catalyzes the transfer of fucose from GDP-Fuc to N-linked type complex glycopeptides, was purified from a culture supernatant of human gastric cancer cell line MKN45. The purification procedures included chromatographies on Q-Sepharose Fast Flow, synthetic GDP-hexanolamine-Sepharose, and GnGn-bi-Asn-Sepharose columns. SDS-PAGE of the purified enzyme gave a major band corresponding to an apparent molecular mass of 60 kDa. The enzyme was recovered in a 12% final yield with an approximately 4,600-fold increase in specific activity. The pH optimum was 7.5, and the enzyme was fully active in the presence of 5 mM EDTA and did not require divalent cations, Mg2+ and Ca2+. Oligonucleotide primers designed from partial amino acid sequences were used to amplify and clone alpha1-6 FucT cDNA from a cDNA library of MKN45 cells. The cDNA encodes 575 amino acids in length, and contains the predicted N-terminal and internal amino acid sequences derived on lysyl endopeptidase digestion. The homology to porcine brain alpha1-6 FucT is 92.2% at the nucleotide level and 95.7% at the amino acid level. No putative N-glycosylation sites were found in the predicted amino acid sequence of the human MKN45 cell enzyme or that of porcine brain. Thus, the enzyme is distinct from other fucosyltransferases which catalyze alpha1-2, alpha1-3, and alpha1-4 fucose addition.

Amino Acid Sequence↗

PubMed1997

CD9 antigen interacts with heparin-binding EGF-like growth factor through its heparin-binding domain.

Heparin/heparan-sulfate proteoglycan (HSPG) binds to heparin-binding epidermal growth factor-like growth factor (HB-EGF) through its heparin-binding domain (HBD), which consists of 21 amino acid residues (P21). The CD9 antigen also interacts with a membrane-anchored form of HB-EGF (proHB-EGF) and enhances its juxtacrine activity. The CD9 antigen potentiates the juxtacrine activity of both proHB-EGF and proamphiregulin, but has no effect on proTGF-alpha. While both HB-EGF and amphiregulin contain an HBD, TGF-alpha does not. This suggests that the HBD of HB-EGF is also involved in CD9 antigen binding. Mutant CHO cells which lack HSPG recovered their capacity to bind to immobilized P21 when transfected with CD9 antigen cDNA. This binding was competitively inhibited by heparin in a dose-dependent manner. The interactions between synthetic peptides corresponding to the extracellular domain of CD9 antigen and the immobilized P21 were analyzed with surface plasmon resonance. The 119VIKEVQEFYKDTYNKLKTKD138 sequence of the CD9 antigen is thought to represent the binding site for HB-EGF. The k(D) values for heparin/P21 and 119V-D138/P21 were (2.82+/-0.10) x 10(-8) M and (3.71+/-0.71) x 10(-5) M, respectively. These results suggest that the 119V-D138 sequence of the CD9 antigen is the site which interacts with the HBD and may play an essential role in the upregulation of the juxtacrine activity of proHB-EGF.

Amino Acid Sequence↗

PubMed1997

A novel brain-derived member of the epidermal growth factor family that interacts with ErbB3 and ErbB4.

A novel member of the epidermal growth factor (EGF) family, the neural- and thymus-derived activator for ErbB kinases (NTAK), has been purified and cloned. Five alternative spliced isoforms have been detected in the rat adrenal pheochromocytoma cell line, PC-12 cells. The rat NTAK alpha2a isoform exhibits 94% identity in its primary sequence with the human NTAK alpha isoform. In vivo, NTAK is only expressed in the brain of rat E11.5 embryos, and in the brain and thymus of adult rats. The soluble 46 kDa form binds directly to ErbB3 and B4, but not to ErbB1 or B2. NTAK, however, transactivates ErbB1 and B2 via heterodimerization with ErbB3 or B4. NTAK stimulates the differentiation of MDA-MB-453 cells and competitively inhibits the binding of [125I]neuregulin to these cells. In addition to these neuregulin-like properties, NTAK exhibits limited structural homology to neuregulins in the immunoglobulin (Ig)-like, EGF-like, and hydrophobic domains. Thus, NTAK appears to be a new member of the EGF family displaying neuregulin properties.

Amino Acid Sequence↗

PubMed1997

Induction of apoptotic cell death in human endothelial cells treated with snake venom: implication of intracellular reactive oxygen species and protective effects of glutathione and superoxide dismutases.

Human vascular endothelial cells play a pivotal role in atherosclerotic changes but are resistant to apoptotic inducers such as Fas ligand and it has been difficult to induce apoptosis. We developed an experimental model for the apoptosis in the endothelial cells by using snake venom treatment. Snake venom was found to generate intracellular reactive oxygen species (ROS) in the endothelial cells, which leads to apoptosis as judged by electron microscopy as well as by DNA cleavage. Buthionine sulfoximine (BSO) and diethyldithiocarbamate (DDC) accelerated the apoptosis, indicating intracellular glutathione and superoxide levels play a critical role. Pretreatment with tumor necrosis factor (TNF) or phorbol ester (TPA), which increases the Mn-SOD level, prevented the apoptosis. These data suggest that intracellular ROS enhances apoptosis whereas several anti-oxidants are protective in human endothelial cells. The induction of apoptosis by ROS of endothelial cells may be related to initiation of atherosclerotic changes.

Animals↗

PubMed1997

Effects of endurance training on superoxide dismutase activity, content and mRNA expression in rat muscle.

1. The purpose of the present study was to investigate the changes in superoxide dismutase (SOD) isoenzyme (Mn(2+)-SOD and Cu2+, Zn(2+)-SOD) activities, contents and mRNA expressions in rat skeletal muscle during endurance training and a single bout of exercise. 2. Thirty-eight male Wistar rats were divided into untrained (U) and trained (T) groups. The T group rats were treadmill-trained for 9 weeks. The activity, content and mRNA expression of Mn(2+)-SOD and Cu2+, Zn(2+)-SOD were determined in the soleus muscle of each rat. 3. Mn(2+)-SOD activity and content in the T group were significantly higher than in the U group, both at rest (22 and 21%, respectively) and after exercise (24 and 46%, respectively), while a single bout of exercise affected neither the activity nor content of Mn(2+)-SOD in either group. 4. The content of Cu2+,Zn(2+)-SOD in both groups was not different at rest and after exercise, although its activity at rest was significantly higher in the T group than in the U group (by 29%). 5. After exercise, the expression of Mn(2+)-SOD mRNA was markedly attenuated only in the U group (49%); the expression of Cu2+,Zn(2+)-SOD mRNA was not influenced by exercise. 6. Our results suggest that adequate endurance training increases both the activity and content of Mn(2+)-SOD and that untrained rats are rather susceptible to oxidative stress during physical exercise. It thus appears that Mn(2+)-SOD provides a reliable index of physical training. 7. The results obtained in the present study also suggest that muscle has the capacity of responding to training in such a manner as to reduce the potential harm arising from the accumulation of oxygen free radicals resulting from enhanced metabolic activity.

Animals↗