Diabetes-associated nitration of tyrosine and inactivation of succinyl-CoA:3-oxoacid CoA-transferase

Turko, Illarion V.; Marcondes, Sisi; Murad, Ferid

doi:10.1152/ajpheart.2001.281.6.h2289

Cited by 183 publications

(157 citation statements)

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“…Total protein was extracted from liver tissue using a Standard protocol in our laboratory. 24 Liver mitochondria were isolated from liver homogenates by differential centrifugation as described by Turko et al 25 Immunoprecipitation of Mitochondrial Proteins and Western Blot Analysis. The immunoprecipitation assays were performed as previously described.…”

Section: Methodsmentioning

confidence: 99%

Effects of rosiglitazone on the liver histology and mitochondrial function in ob/ob mice†

et al. 2007

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Insulin resistance is present in almost all patients with nonalcoholic steatohepatitis (NAFLD), and mitochondrial dysfunction likely plays a critical role in the progression of fatty liver into nonalcoholic steatohepatitis. Rosiglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPAR␥), is an insulin sensitizer drug that has been used in a number of insulin-resistant conditions, including NAFLD. The aim of this study was to analyze the effects of rosiglitazone on the liver histology and mitochondrial function in a model of NAFLD. All studies were carried out in wild-type and leptin-deficient (ob/ob) C57BL/6J mice. Ob/ob mice were treated with 1 mg/kg/day, and activity of mitochondrial respiratory chain (MRC), beta-oxidation, lipid peroxidation, glutathione content in mitochondria, and 3-tyrosine-nitrated proteins in mitochondria were measured. In addition, histological and ultrastructural changes induced by rosiglitazone were also noted. Rosiglitazone treatment increased liver steatosis, particularly microvesicular steatosis. In these animals, mitochondria were markedly swollen with cristae peripherally placed. In ob/ob mice, this drug increased PPAR␥ protein expression and lipid peroxide content in liver tissue and decreased glutathione concentration in mitochondria. Rosiglitazone suppressed the activity of complex I of the MRC in ob/ob mice, but did not affect beta-oxidation. 3-Tyrosine nitrated mitochondrial proteins, significantly increased in ob/ob mice, were not modified by rosiglitazone treatment. Conclusion: Treatment of ob/ob mice with rosiglitazone did not reverse histological lesions of NAFLD or improve MRC activity. On the contrary, rosiglitazone reduced activity of complex I and increased oxidative stress and liver steatosis.

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Section: Methodsmentioning

confidence: 99%

Effects of rosiglitazone on the liver histology and mitochondrial function in ob/ob mice†

et al. 2007

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“…Even though biological nitration yields are relatively low (100 -500 mol of nitrotyrosine/mol of tyrosine under inflammatory conditions) (2), they are an established marker for the extent of the production of nitric oxide ( ⅐ NO) 1 -derived reactive species during both physiological and pathological conditions. Cumulative protein tyrosine nitration, manifesting through multiple mechanisms, may be actively involved in the onset and/or progression of various diseases with an inflammatory component and associated with increased levels of reactive oxygen species and ⅐ NO (1,(3)(4)(5)(6)(7). Cumulative protein tyrosine nitration may also be involved in the pathogenesis of acute pathological conditions such as ischemia-reperfusion (8,9).…”

mentioning

confidence: 99%

“…1) (14). The resulting high probability of protein nitration, especially in the mitochondrial matrix (15), is reflected by the fact that a substantial number of the proteins identified as nitrated in vivo are localized in mitochondria (6,7).…”

mentioning

confidence: 99%

“…To be considered a cellular signaling mechanism, protein nitration must meet four basic criteria: controlled rates of formation, specificity, modification of target protein and cell function, and reversibility (16). The specificity of protein nitration and modification of protein and cell functions by protein nitration have been demonstrated (1,7,15,16); however, very little evidence exists regarding the reversibility by a protein "denitration" process in vivo (1,16,17). We recently discovered that isolated rat liver mitochondria are capable of nitrotyrosine clearance during a 20-min episode of hypoxia-anoxia and that nitrotyrosine immunoreactivity reappears during reoxygenation in an L-arginine-dependent way at protein spots that matched the spots before hypoxia-anoxia (18).…”

mentioning

confidence: 99%

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Rapid and Selective Oxygen-regulated Protein Tyrosine Denitration and Nitration in Mitochondria

Koeck

Hazen

et al. 2004

Journal of Biological Chemistry

167

133

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Growing evidence connects a cumulative formation of 3-nitrotyrosyl adducts in proteins as a marker for oxidative damage with the pathogenesis of various diseases and pathological conditions associated with oxidative stress. A physiological signaling role for protein nitration has also been suggested. Controlled "denitration" would be essential for such a contribution of protein nitration to cellular regulatory processes. Thus, we further characterized such a potentially controlled, reversible tyrosine nitration that occurs in respiring mitochondria during oxygen deprivation followed by reoxygenation, which we recently discovered. Mitochondria constitute cellular centers of protein nitration and are leading candidates for a "nitrative" regulation. Mitochondria are capable of completely eliminating 3-nitrotyrosyl adducts during 20 min of hypoxia-anoxia and undergoing a selective partial reduction after only 5 min. This denitration is independent of protein degradation but depends on the oxygen tension. Reoxygenation re-establishes protein tyrosine nitration patterns that are almost identical to the pattern that occurs before hypoxia-anoxia, with nitration levels that depend on the duration of hypoxia-anoxia. The identified mitochondrial targets of this process are critical for energy and antioxidant homeostasis and, therefore, cell and tissue viability. This cycle of protein nitration and denitration shows analogies to protein phosphorylation, and we demonstrate that the cycle meets most of the criteria for a cellular signaling mechanism. Taken together, our data reveal that protein tyrosine nitration in mitochondria can be controlled, is target-selective and rapid, and is dynamic enough to serve as a nitrative regulatory signaling process that likely affects cellular energy, redox homeostasis, and pathological conditions when these features become disturbed.

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“…NO is normally produced from L-arginine by endothelial Nitric Oxide Synthase (eNOS) in the vasculature (Turko et al, 2001). NO mediates endothelium-dependent vasorelaxation by its action on guanylate cyclase in Vascular Smooth Muscle Cells (VSMC), initiating a cascade that leads to vasorelaxation (Vega-Lopez et al, 2004).…”

Section: Ajptmentioning

confidence: 99%

Remedial Effects of Vitamin E and L-Arginine on Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats

Bin-Jaliah¹

2014

American Journal of Pharmacology and Toxicology

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It was shown that hyperglycemia in diabetic patients is the main factor of diabetic peripheral neuropathies. Various pathways related to oxidative stress, vascular defect and defective endothelium dependent relaxation have been implicated in the development of diabetic peripheral neuropathy. A substantial number of studies have shown that antioxidant treatment are promising therapeutics that can prevent or correct reduced motor nerve conduction in diabetic rats by acting on these mechanisms. This study was designed to investigate the possible role of insulin treatment along with or without vitamin E or L-arginine on diabetic neuropathy. This goal was accessed by examining nerve conduction, parameters of oxidative stress and lipid peroxidation as well as the expression level of endothelial nitric oxide synthase in the sciatic nerve of control and streptozotocine-induced diabetic rats. Data showed that diabetic rats showed increased levels of serum glucose (382.5%) and sciatic nerve lipid peroxidation Marker (MDA, 261.6%) with a concomitant decrease in the expression of sciatic nerve eNOS mRNA as compared to control rats. The nerve conduction studies of the sciatic nerves of these rats showed decrease conduction as evident by delayed NCV (63.6%) and low Amplitude of Muscle Contraction (AMC, 36.4%). Solitary insulin treatment (but not vitamin-E or L-arginine) corrected serum glucose to control values and corrected nerve conduction parameters in the sciatic nerve. However, treating diabetic rats with different doses of vitamin E (300 mg kg −1 and 600 mg kg −1 ) significantly reduced oxidative stress by decreasing MDA and increasing GPx activity, corrected NCV by reducing the latency and improving AMC and increased eNOS mRNA expression in sciatic nerve with a more profound effect to seen with the high dose (600 mg kg −1 ). However, the maximum potent ameliorating effect of the vitamin E on these parameters was seen when administered in combination with insulin. On the other hand, L-arginine treatment alone or in combination with insulin had no effect on the oxidative stress markers nor eNOS expression but significantly and maximally improved NCV through reducing the conduction latency and increasing AMC. This study supported the notion that diabetic peripheral neuropathy is a multifactorial complication, caused by hyperglycemia, oxidative stress and vascular impairment. It is concluded that conjugate treatment with vitamin-E, especially in higher doses, with insulin could be of great value. Moreover correction of impaired nerve blood flow by drugs that induce nitric oxide has proved to be efficient in the protection against and correction of experimental diabetic peripheral neuropathy.

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Diabetes-associated nitration of tyrosine and inactivation of succinyl-CoA:3-oxoacid CoA-transferase

Cited by 183 publications

References 41 publications

Effects of rosiglitazone on the liver histology and mitochondrial function in ob/ob mice†

Effects of rosiglitazone on the liver histology and mitochondrial function in ob/ob mice†

Rapid and Selective Oxygen-regulated Protein Tyrosine Denitration and Nitration in Mitochondria

Remedial Effects of Vitamin E and L-Arginine on Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats

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