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PubMed1993

Homocysteine metabolism and the oxidative modification of proteins and lipids.

Altered homocysteine metabolism is implicated as a pathogenic factor in atherogenesis, neoplasia, and aging. Hereditary enzymatic deficiencies and nutritional deficiencies of folate, pyridoxine, or cobalamin are associated with elevated blood homocysteine, accelerated atherosclerosis, and manifestations of aging. The failure of malignant cells to metabolize homocysteine thiolactone to sulfate is attributed to deficiency of thioretinaco, a complex containing cobalamin, homocysteine thiolactone, and retinoic acid. The sulfhydryl group of homocysteine is believed to act catalytically with ferric or cupric ions in a mixed function oxidation system to generate hydrogen peroxide, oxygen radicals, and homocysteinyl radicals. These reactive species may interact with the active site of enzyme protein to cause inactivation of catalytic activity. Homocysteine thiolactone is oxidized to sulfate by a process involving ascorbate, thioretinamide, and superoxide, under the control of thyroxine and growth hormone. Thioretinaco is believed to be the active site of adenosine triphosphate (ATP) binding in oxidative phosphorylation with the participation of oxygen, ascorbate, proton gradient, and electron transport. Depletion of thioretinaco from mitochondrial and microsomal membranes may be associated with increased formation and release of radical oxygen species within neoplastic and senescent cells. Specific proposals are made for investigating the importance of homocysteine metabolism in the oxidative modification of proteins and lipids.

Aging↗
PubMed1987

Kinetics of cholesterol and phospholipid exchange between mycoplasma membranes and lipid vesicles.

The following modifications in the lipid composition of Mycoplasma gallisepticum or M. capricolum membranes led to changes in the rates of [14C]cholesterol and [14C]phospholipid exchange between cell membranes and an excess of small unilamellar vesicles: 1) increase in the cholesterol/phospholipid molar ratio from 0.25 to 0.92; 2) incorporation of synthetic, cross-linked phosphatidylethanolamine (PE) derivatives, 3) incorporation of sphingomyelin (SPM); and 4) increase in the phosphatidylglycerol/cardiolipin ratio of M. capricolum cell membranes by supplementing the growth medium with 0.5 mM CaCl2 CaCl2, and decrease in this ratio by supplementing the growth medium with 0.5 mM CaCl2 and 20 micrograms/ml egg phosphatidylcholine or with isopalmitic acid. The rates of radiolabeled lipid exchange decreased when the content of cholesterol, cross-linked PE, or SPM increased, indicating an inverse correlation between exchange rate and membrane lipid order. This is consistent with an exchange mechanism that involves the slow dissolution of the lipid from the surface of the donor particle. Lipidic particles appeared in trypsin-treated M. capricolum membranes obtained from cells grown with both Ca2+ and PC, whereas the hexagonal-II phase appeared in membranes from cells grown with Ca2+. Cholesterol and phospholipid exchange rates were enhanced under the conditions in which the bilayer structure was destabilized by transitional states between the lamellar and hexagonal-II phases. Thus, mycoplasmas are well suited for examination of the influence of membrane lipid composition on rates of lipid exchange between membranes.

Calcium Chloride↗
PubMed1996

Different effects of thiol and nonthiol ace inhibitors on copper-induced lipid and protein oxidative modification.

Differences among angiotensin-converting enzyme inhibitors (ACEI) in scavenging reactive oxygen species were described and mainly attributed to the presence or absence of a thiol group. Plasma constituents and red cells are known targets for oxidative damage. Transition metals, like copper, are well known catalizers of free radical generation. In the present study we compared the abilities of captopril (a thiol ACEI), enalaprilat, and lisinopril (two nonthiol ACEI) for inhibiting copper-induced thiobarbituric acid reactive substances (TBARS) formation and fluorescence generation in whole human plasma and low-density lipoprotein. The effects of those ACEI on copper/hydrogen peroxide-induced fluorescence development and electrophoretic mobility modification in albumin and on copper-induced TBARS formation and hemolysis in human red cells were also compared. Captopril was more effective than the two nonthiol ACEI in inhibiting plasma and LDL lipid peroxidation, but it was ineffective in inhibiting the albumin oxidative modification that was moderately inhibited by enalaprilat and lisinopril. On the contrary, the inhibitory effects of the three ACEI on copper-induced lipid peroxidation and hemolysis in red cell suspensions were more uniform. This as yet unreported red cell protective effect may deserve pharmacological evaluation. Our results show that captopril is a more effective antioxidant than the nonthiol ACEI in some systems. However, the nonthiol ACEI also have the ability to partially protect some targets against oxidative damage. These observations suggest that the presence of a thiol group in the ACEI structure is not the only determinant for the antioxidant properties.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Modification of the adipocyte lipid binding protein by sulfhydryl reagents and analysis of the fatty acid binding domain.

The adipocyte lipid binding protein (ALBP) is a member of a multigene family of low molecular weight proteins which stoichiometrically and saturably bind hydrophobic ligands and presumably facilitate intracellular lipid metabolism. To probe the structure-function relationship of the binding domain of ALBP, chemical modification has been employed. Modification of the two cysteinyl residues of ALBP (Cys1 and Cys117) with a variety of sulfhydryl reagents decreased the apparent affinity for oleic acid in the following order of effectiveness: methyl methanethiosulfonate much much less than p-(chloromercuri)benzenesulfonic acid less than N-ethylmaleimide (NEM) = 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). Thiol titration of ALBP with DTNB in the presence of bound oleate resulted in the modification of a single cysteinyl residue. The oleate-protected cysteine was identified as Cys117 by modification with a combination of reversible (DTNB) and irreversible (NEM) sulfhydryl reagents in the presence or absence of saturating oleic acid. Cys117-NEM ALBP exhibited a large decrease in binding affinity while Cys1-NEM ALBP exhibited normal binding properties. Neither the modification of ALBP with NEM nor the addition of oleic acid had a significant effect on protein structure, as judged by circular dichroic analysis. These results suggest that Cys117 of ALBP resides in the ligand binding domain and that site-specific modification can be utilized to assess the conformational flexibility of the binding cavity.

Amino Acid Sequence↗
PubMed2005

Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia.

Hyperglycemia causes the autoxidation of glucose, glycation of proteins, and the activation of polyol metabolism. These changes accelerate generation of reactive oxygen species (ROS) and increases in oxidative chemical modification of lipids, DNA, and proteins in various tissues. Oxidative stress may play an important role in the development of complications in diabetes such as lens cataracts, nephropathy, and neuropathy. Glycation reactions, especially Maillard reactions, occur in vivo as well as in vitro and are associated with the chronic complications of diabetes mellitus and aging and age-related diseases by increases in oxidative chemical modification of lipids, DNA, and proteins. In particular, long-lived proteins such as lens crystallines, collagens, and hemoglobin may react with reducing sugars to form advanced glycation end products (AGEs). Recently, we found a novel type of AGE, named MRX, and we found that MRX is a good biomarker for detecting oxidative stress produced during Maillard reaction. We also examined in detail the role of lipid peroxidation reaction in hyperglycemia and found that hexanoyl modification formed by the reaction of oxidized lipids and proteins must be important for oxidative stress. Detailed analyses of the formation mechanism of hexanoyl lysine (HEL) moiety in proteins were conducted, and excretion of HEL into urine was quantified by using LC/MS/MS. Macrophages and neutrophils play an important role in oxidative stress during hyperglycemia, and we determined that oxidatively modified tyrosines are a good biomarker for formation of oxidative stress at an early stage. Immunochemical analyses by application of monoclonal antibodies specific to lipid hydroperoxide-modified proteins produced by polyunsaturated fatty acids including docosahexaenoic acid (DHA) in oxidative stress caused by hyperglycemia were conducted, and the relationship between glycation and lipid peroxidation reactions both by chemical and immunochemical approaches are discussed. Recently, we put much more focus on dietary antioxidants for prevention of diabetic complications. Curcuminoids, the main yellow pigments in Curcuma longa (turmeric), have been used widely and for a long time in the treatment of sprain and inflammation in indigenous medicine. Curcumin is the main component of turmeric, and two minor components are also present as the curcuminoids. Curcuminoids possess antioxidant activity. Protective effects of curcumin (U1) and one of its major metabolites, tetrahydrocurcumin (THU1), have been examined for development of diabetic cataract in 25% galactose-fed SD rats. Through detailed examination of protective mechanisms of THU1, it was found that THU1 showed that scavenger ROS not only formed during hyperglycemia, but also induced antioxidative enzymes including detoxification enzymes such as glutathine S-transferase. THU1 also showed significant increase of glutathione concentration in the cultured rat lens. Glutathione (gamma-glutamylcysteinyl glycine [GSH]) is thought to be an important factor in cellular function and defense against oxidative stress, and we found that dietary GSH suppresses oxidative stress in vivo in prevention of diabetic complications such as diabetic nephropathy and neuropathy.

Animals↗
PubMedDate not supplied

Lipid-modified proteins as biomarkers for cardiovascular disease: a review.

Lipid-modified proteins are classified based on the identity of the attached lipid, a post- or co-translational modification required for their biological function. At least five different lipid modifications of cysteines, glycines and other residues on the COOH- and NH(2)-terminal domains have been described. Cysteine residues may be modified by the addition of a 16-carbon saturated fatty acyl group by a labile thioester bond (palmitoylation) or by prenylation processes that catalyze the formation of thioether bond with mevalonate derived isoprenoids, farnesol and geranylgeraniol. The NH(2)-terminal glycine residues may undergo a quite distinct process involving the formation of an amide bond with a 14-carbon saturated acyl group (myristoylation), while glycine residues in the COOH-terminal may be covalently attached with a cholesterol moiety by an ester bond. Finally, cell surface proteins can be anchored to the membrane through the addition of glycosylphosphatidylinositol moiety. Several lines of evidence suggest that lipid-modified proteins are directly involved in different steps of the development of lesions of atherosclerosis, from leukocyte recruitment to plaque rupture, and their expression or lipid modification are likely altered during atherogenesis. This review will briefly summarize the different enzymatic pathways of lipid modification and propose a series of lipid-modified proteins that can be used as biomarkers for cardiovascular disease.

Acyltransferases↗
PubMed1999

Formation of Nepsilon-(hexanonyl)lysine in protein exposed to lipid hydroperoxide. A plausible marker for lipid hydroperoxide-derived protein modification.

The objectives of this study were to estimate the structure of the lipid hydroperoxide-modified lysine residue and to prove the presence of the adducts in vivo. The reaction of lipid hydroperoxide toward the lysine moiety was investigated employing N-benzoyl-glycyl-L-lysine (Bz-Gly-Lys) as a model compound of Lys residues in protein and 13-hydroperoxyoctadecadienoic acid (13-HPODE) as a model of the lipid hydroperoxides. One of the products, compound X, was isolated from the reaction mixture of 13-HPODE and Bz-Gly-Lys and was then identified as N-benzoyl-glycyl-Nepsilon-(hexanonyl)lysine. To prove the formation of Nepsilon-(hexanonyl)lysine, named HEL, in protein exposed to the lipid hydroperoxide, the antibody to the synthetic hexanonyl protein was prepared and then characterized in detail. Using the anti-HEL antibody, the presence of HEL in the lipid hydroperoxide-modified proteins and oxidized LDL was confirmed. Furthermore, the positive staining by anti-HEL antibody was observed in human atherosclerotic lesions using an immunohistochemical technique. The amide-type adduct may be a useful marker for the lipid hydroperoxide-derived modification of biomolecules.

Humans↗
PubMed1992

Oat lipids-induced covalent DNA modifications (I-compounds) in female Sprague-Dawley rats, as determined by 32P-postlabeling.

Previous studies have shown that the presence of oats in the diet contributes to formation of I-compounds (age-dependent covalent DNA modifications detected by 32P-postlabeling assay) in female Sprague-Dawley rat liver DNA. The current study explored the possible ingredients in oats responsible for the observed effects on DNA. Feeding AIN-76A diet containing 5% oat lipids (obtained by methanol extraction and dissolved in trioctanoin) in place of corn oil for 2 months successfully induced the formation of 3 oats-specific (spots 2-4) and 4 natural ingredient diet-specific I-compounds (spots 6-9) in liver DNA. Barley, an oatlike cereal, induced 3 of these spots at very low intensities but not the 3 oats-specific I-spots. Oral administration of oat lipids to weanling rats of both sexes for 7 days elicited trace amounts of the oats-specific spots and spot 9 in liver DNA. However, when oat lipids were given at 6 or 9 weeks of age, the oats-specific spots were detected at high levels in female but not in male rats. These oats-related DNA modifications were also present in 6-week-old female rats which had received oat lipids p.o. for 2 or 3 days or i.p. for 4 days. Rats given trioctanoin or extracts from natural ingredient Wayne diet (lacking oats) did not show any of these spots. On the other hand, rats treated with extracts from an oats-containing Teklad diet displayed a trace amount of one of these I-compounds. Oat lipids did not induce any extra spots in rat kidney DNA. Feeding of AIN diet supplemented with oats to female Syrian hamsters did not elicit any renal or hepatic DNA alterations, as detected by 32P-postlabeling. Rats fed oat lipids-supplemented AIN diet or Purina diet showed the highest levels of I-compounds overall in liver among all dietary groups and these two groups also had significantly higher hepatic DNA synthesis rates. Oat lipids enhanced kidney DNA synthesis also. The total hepatic or renal cytochrome P-450 contents were not significantly affected by different diets. These results demonstrate a novel link between a natural dietary ingredient and covalent DNA modifications and shed light on the origins of certain I-compounds.

Animals↗
PubMed2000

A PhoP/PhoQ-induced Lipase (PagL) that catalyzes 3-O-deacylation of lipid A precursors in membranes of Salmonella typhimurium.

Pathogenic bacteria modify the structure of the lipid A portion of their lipopolysaccharide in response to environmental changes. Some lipid A modifications are important for virulence and resistance to cationic antimicrobial peptides. The two-component system PhoP/PhoQ plays a central role in regulating lipid A modification. We now report the discovery of a PhoP/PhoQ-activated gene (pagL) in Salmonella typhimurium, encoding a deacylase that removes the R-3-hydroxymyristate moiety attached at position 3 of certain lipid A precursors. The deacylase gene (pagL) was identified by assaying for loss of deacylase activity in extracts of 14 random TnphoA::pag insertion mutants. The pagL gene encodes a protein of 185 amino acid residues unique to S. typhimurium and closely related organisms such as Salmonella typhi. Heterologous expression of pagL in Escherichia coli on plasmid pWLP21 results in loss of the R-3-hydroxymyristate moiety at position 3 in approximately 90% of the lipid A molecules but does not inhibit cell growth. PagL is synthesized with a 20-amino acid N-terminal signal peptide and is localized mainly in the outer membrane, as judged by assays of separated S. typhimurium membranes and by SDS-polyacrylamide gel analysis of membranes from E. coli cells that overexpress PagL. The function of PagL is unknown, given that S. typhimurium mutants lacking pagL display no obvious phenotypes, but PagL might nevertheless play a role in pathogenesis if it serves to modulate the cytokine response of an infected animal host.

Acylation↗
PubMed1975

Structure and synthesis of a lipid-containing bacteriophage. Chemical modifications of bacteriophage PM2 and the resulting alterations in acyl-chain motion in the PM2 membrane.

The nucleocapsid proteins of bacteriophage PM2 and the inner lamella of the lipid bilayer, containing most of the phosphatidlethanolamine residues, were selectively cross-linked in the presence of 0.1-0.5% glutaraldehyde, 5 mM dimethylsuberimidate, or 0.05% toluene 2,4-diisocyanate. The biological activity (p.f.u.) of PM2 modified by these reagents decreased 10(6)-fold in all cases. The spike and coat proteins were selectively cross-linked in the presence of 7.5 mM N,N'-p-phenylenedimaleimide. The biological activity of virus modified by this reagen was unaffected. The electron paramagnetic resonance spectra of fatty acid spin labels incorporated into native and chemically modified viral membranes were qualitatively similar but show quantitative differences. Fixation with glutaraldehyde increased the rigidity of the membrane while Triton X-100 induced a more flexible structure. There was no change in the electron paramagnetic resonance spectrum of virus treated with N,N'-p-phenylenedimaleimide, however.

Bacteriophages↗
PubMed2004

Prediction of sequence signals for lipid post-translational modifications: insights from case studies.

In silico annotation techniques for post-translational modifications (PTMs) are important to generate biologically meaningful descriptions for sequences of experimentally uncharacterized proteins. Having previously contributed with predictors for lipid PTMs, we summarize our methodological experience. Rather than only looking for the sequence pattern in substrate sequences, a strategy aimed at creating a generalized model of substrate protein/enzyme interaction appears more appropriate since the number of known substrate sequences is small, and some of them are not sufficiently verified experimentally. Such a physical approach (in contrast to a mere textual analysis of substrate sequences) can also take into account other, heterogeneous biological data (mutations of substrate sequences, kinetic data, enzyme sequences/structures) with simple analytical expressions in the score function. Several lipid PTMs are encoded in the form of a small sequence region (with pronounced amino acid type preferences) that is connected to the substrate protein by a linker region with many conformationally flexible, hydrophilic residues. A score function composed of terms penalizing sequence properties known to be incompatible with productive substrate protein/enzyme complexes essentially unselects inappropriate queries. Also, we estimate the number of nonredundant sequences necessary for robust profile computation with statistical criteria, a number that is not reached in most cases of PTM prediction. Finally, we discuss the usage of evolutionary information in evaluating the functional importance of predicted PTMs in cases of motif conservation within sequence families.

Acetyltransferases↗
PubMed1982

Growth Temperature-Induced Alterations in the Thermotropic Properties of Nerium oleander Membrane Lipids.

The temperature boundary for phase separation of membrane lipids extracted from Nerium oleander leaves was determined by analysis of spin label motion using electron spin resonance spectroscopy and by analysis of polarization of fluorescence from the probe, trans-parinaric acid. A discontinuity of the temperature coefficient for spin label motion, and for trans-parinaric acid fluorescence was detected at 7 degrees C and -3 degrees C with membrane lipids from plants grown at 45 degrees C/32 degrees C (day/night) and 20 degrees C/15 degrees C, respectively. This change was associated with a sharp increase in the polarization of fluorescence from trans-parinaric acid indicating that significant domains of solid lipid form below 7 degrees C or -3 degrees C in these preparations but not above these temperatures. In addition, spin label motion indicated that the lipids of plants grown at low temperatures are more fluid than those of plants grown at higher temperatures.A change in the molecular ordering of lipids was also detected by analysis of the separation of the hyperfine extrema of electron spin resonance spectra. This occurred at 2 degrees C and 33 degrees C with lipids from the high and low temperature grown plants, respectively. According to previous interpretation of spin label data the change at 29 degrees C (or 33 degrees C) would have indicated the temperature for the initiation of the phase separation process, and the change at 7 degrees C (or -3 degrees C) its completion. Because of the present results, however, this interpretation needs to be modified.Differences in the physical properties of membrane lipids of plants grown at the hot or cool temperatures correlate with differences in the physiological characteristics of plants and with changes in the fatty acid composition of the corresponding membrane lipids. Environmentally induced modification of membrane lipids could thus account, in part, for the apparently beneficial adjustments of physiological properties of this plant when grown in these regimes.

Journal Article↗
PubMed1995

Formation of F2-isoprostanes during oxidation of human low-density lipoprotein and plasma by peroxynitrite.

F2-Isoprostanes are novel bioactive prostaglandin F2-like compounds produced by nonenzymatic free radical-catalyzed peroxidation of arachidonic acid. F2-Isoprostanes are initially formed in situ on phospholipids and subsequently released. Quantification of the F2-isoprostanes has been found to represent a valuable and reliable marker of lipid peroxidation. Oxidative modification of low-density lipoprotein (LDL) is a key process for the recognition of LDL by the scavenger receptors on macrophages. The oxidative mechanism responsible for the modification of LDL in vivo remains unclear, but an attractive candidate is the powerful oxidant peroxynitrite, which can be formed by reaction of nitric oxide and superoxide in the vessel wall. To further explore the potential role of peroxynitrite in the oxidative modification of plasma lipids, we investigated whether incubation of LDL and plasma with peroxynitrite or SIN-1, which decomposes to form nitric oxide and superoxide, catalyzes the formation of F2-isoprostanes. Incubation of LDL with peroxynitrite (0.125 to 1 mmol/L) or SIN-1 (0.5 and 1 mmol/L) induced a concentration-dependent increase in the formation of F2-isoprostanes, reaching a maximum of 5.5 +/- 2.05-fold (SEM) and 18.2 +/- 4.0-fold above control values, respectively. The increase of F2-isoprostanes induced by SIN-1 was essentially completely inhibited by superoxide dismutase. Incubation of plasma with peroxynitrite or SIN-1 yielded similar results. These results indicate that peroxynitrite can induce the formation of F2-isoprostanes in lipoproteins. Since F2-isoprostanes can exert potent biological activity such as vasoconstriction, they may contribute to the vascular pathobiology associated with atherosclerosis.

Antihypertensive Agents↗
PubMed1998

Keratin modifications and solubility properties in epithelial cells and in vitro.

The gains that have been made in characterizing some of the keratin posttranslational modifications have helped answer some questions regarding these modifications and have generated an information base for asking additional refined questions in future studies. Highlights of where we believe we currently stand with regard to keratin posttranslational modifications are as follows: 1. Keratin glycosylation, via O-GlcNAc, is a dynamic modification that has been conclusively identified in K13, K8, and K18. Three serine glycosylation sites in the head domain of K18 have been identified, and it is possible that all keratins are glycosylated. The function of this modification remains to be defined, but is likely to be different from phosphorylation, since the two modifications are generally segregated on different molecules and several examples exist whereby both modifications increase simultaneously. 2. Keratin phosphorylation occurs within the tail and/or head domains of all keratins that have been examined. Several serine phosphorylation sites and some of the relevant kinases have been characterized in K8, K6, and K18, and serine/threonine sites have been identified in K1. Functions of keratin phosphorylation that have significant experimental support include a role in filament solubility and reorganization and a role in regulating keratin binding with other cytoplasmic proteins. The significance of filament reorganization and increased solubility under a variety of physiologic conditions such as mitosis and cell stress are important areas of future and ongoing investigation. Other associations with keratin phosphorylation include protection against cell stress, cell signaling, apoptosis, and cell compartment-specific roles. At this stage, however, it is not known if these associations play direct or indirect roles. 3. Keratin transglutamination occurs in epidermal and simple epithelial keratins under physiologic and pathologic states, respectively. In the physiological context, the role of this modification is clear in terms of providing a compact protective structure, while in the pathologic context of liver disease the role remains ambiguous. 4. Proteolysis of K18 and K19 by caspases occurs during apoptosis, and generates stable keratin fragments that are highly enriched within the cytoskeletal compartment. Proteolysis of the type II keratins appears to be spared for reasons that remain to be defined. It is likely that this apoptosis-associated degradation involves all type I keratins. Keratin fragments are also noted in sera of patients in association with a variety of epithelial tumors. If a signal does exist for the apoptosis-associated fragmentation, aside from caspase activation, then it appears that the overall increase in keratin phosphorylation during apoptosis does not account for this signal. 5. Keratins undergo several other posttranslational modifications including disulfide bond formation (not found in K8/18 due to lack of cystienes) and acetylation of their N-terminal serines. Modification by lipids is also possible, but this modification requires further confirmation. 6. Keratin solublility is highly dynamic and varies profoundly depending on the keratin pair and the physiologic state of the cell. Within the keratin family, simple epithelial keratins are among the most soluble (approximately 5% of K8/18 is soluble at basal conditions). Phosphorylation plays an important role in modulating keratin solubility, and distinct differences occur in site-specific phosphorylation depending on the soluble versus cytoskeletal partitioning of the keratin. Keratin solubility (at least for K8/18) also appears to be regulated by 14-3-3 proteins via K18 Ser33 phosphorylation.

Acetylation↗
PubMed2000

Changed cellular membrane lipid composition and lipid peroxidation of kidney in rats with chronic fluorosis.

An animal model of chronic fluorosis was produced by subjecting Wistar rats to high doses of fluoride in drinking water for a prolonged period. Phospholipid and neutral lipid contents in rat kidney were then analyzed by high-performance liquid chromatography (HPLC), and fatty acid compositions from individual phospholipids were measured by gas chromatography. Lipid peroxidation was detected by the thiobarbituric-acid-reactive substance assay. Results showed that the total phospholipid content significantly decreased in the kidney of the rats treated with high doses of fluoride and the main species influenced were phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Decreased proportions of polyunsaturated fatty acids were observed in PE and PC in kidney of fluoride-treated animals compared to controls. No changes could be detected in the amounts of cholesterol and dolichol in kidneys between the rats treated with fluoride and controls. A significant decrease of ubiquinone in rat kidney was observed in the groups treated with excessive fluoride. High levels of lipid peroxidation were detected in kidney of the rats with fluorosis. It is plausible that the specific modification of lipid composition results from lipid peroxidation. The oxidative stress and modification of cellular membrane lipids may be involved in the pathogenesis of chronic fluorosis and provide a possible explanation for the gross system damage observed in the body, especially in soft tissues and organs.

Animals↗
PubMed1992

Aminoguanidine inhibits the modification of proteins by lipid peroxidation derived aldehydes: a possible antiatherogenic agent.

The reaction of protein amino groups with lipid-peroxidation-derived aldehydes (LPDA) has been shown to play a key role in various pathological processes. Especially important is the reaction of LPDA with apolipoprotein B during oxidative modification of low density lipoprotein (LDL), which leads to its enhanced uptake by macrophages and, eventually, to atherogenesis. Since aminoguanidine, a drug which inhibits the advanced steps of glycation (probably by trapping reactive sugar-derived aldehydes), has been proposed as a therapeutic agent for the prevention of late diabetic complications, we have tested its ability to interfere with the modification of proteins by LPDA. LDL was incubated with cupric ions. Aminoguanidine at 5, 10 and 25 mM inhibited both the increase in electrophoretic mobility of LDL and the generation of thiobarbituric acid reactive substances (TBARS) (P < 0.001). It also inhibited the increase in electrophoretic mobility and 260-400 nm absorbance of bovine serum albumin incubated with malondialdehyde. These results suggest that aminoguanidine may have an antiatherogenic effect.

Aldehydes↗