Role of protein tyrosine nitration in neurodegenerative diseases and atherosclerosis

Lee, J.; Kim, Jae Kyung; Lee, Soo Jae; Kim, Kwang Pyo

doi:10.1007/s12272-009-1802-0

Cited by 67 publications

(53 citation statements)

References 75 publications

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“…In contrast to this, ATF3 strongly inhibited GCK nitration in ethanol-cotreated cells (lane 6), despite the fact that ethanol-induced iNOS expression did not change by ATF3, which may be due to the almost complete reduction of GCK protein expression by ethanol and ATF3 combination. Previous studies have demonstrated that protein nitration may cause a functional loss of many proteins through inhibition of critical Tyr residues on the nitrated proteins (47). GCK activity to convert glucose to glucose-6-phosphate was also inhibited by ethanol or SIN-1, which was reversibly restored by L-NMMA, UA, and deferoxamine (Fig.…”

Section: Discussionmentioning

confidence: 78%

Chronic Ethanol Consumption-induced Pancreatic β-Cell Dysfunction and Apoptosis through Glucokinase Nitration and Its Down-regulation

Kim

Song

Lee

et al. 2010

Journal of Biological Chemistry

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Chronic ethanol consumption is known as an independent risk factor for type 2 diabetes, which is characterized by impaired glucose homeostasis and insulin resistance; however, there is a great deal of controversy concerning the relationships between alcohol consumption and the development of type 2 diabetes. We investigated the effects of chronic ethanol consumption on pancreatic ␤-cell dysfunction and whether generated peroxynitrite participates in the impaired glucose homeostasis. Here we show that chronic ethanol feeding decreases the ability of pancreatic ␤-cells to mediate insulin secretion and ATP production in coordination with the decrease of glucokinase, Glut2, and insulin expression. Specific blockade of ATF3 using siRNA or C-terminally deleted ATF3(⌬C) attenuated ethanol-induced pancreatic ␤-cell apoptosis or dysfunction and restored the down-regulation of glucokinase (GCK), insulin, and pancreatic duodenal homeobox-1 induced by ethanol. GCK inactivation and down-regulation were predominantly mediated by ethanol metabolism-generated peroxynitrite, which were suppressed by the peroxynitrite scavengers N ␥ -monomethyl-L-arginine, uric acid, and deferoxamine but not by the S-nitrosylation inhibitor DTT, indicating that tyrosine nitration is the predominant modification associated with GCK down-regulation and inactivation rather than S-nitrosylation of cysteine. Tyrosine nitration of GCK prevented its association with pBad, and GCK translocation into the mitochondria results in subsequent proteasomal degradation of GCK following ubiquitination. This study identified a novel and efficient pathway by which chronic ethanol consumption may induce GCK down-regulation and inactivation by inducing tyrosine nitration of GCK, resulting in pancreatic ␤-cell apoptosis and dysfunction. Peroxynitrite-induced ATF3 may also serve as a potent upstream regulator of GCK down-regulation and ␤-cell apoptosis.

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Section: Discussionmentioning

confidence: 78%

Chronic Ethanol Consumption-induced Pancreatic β-Cell Dysfunction and Apoptosis through Glucokinase Nitration and Its Down-regulation

Kim

Song

Lee

et al. 2010

Journal of Biological Chemistry

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“…[1][2][3] Recently, the novel nitrosative modification on tyrosine residues, which is the introduction of a nitroso group (-NO) on tyrosine residues by peroxynitrite and tetranitromethane (TNM), has been reported. 4 Protein tyrosine nitration exhibits a certain degree of selectivity, as not all tyrosine residues of proteins are the substrates for nitration.…”

Section: Introductionmentioning

confidence: 99%

Mass Spectrometry Analysis of In Vitro Nitration of Carbonic Anhydrase II

Lee¹,

Kang²,

Cho³

et al. 2014

Bulletin of the Korean Chemical Society

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Protein tyrosine nitration is considered as an important indicator of nitrosative stresses and as one of the main factors for pathogenesis of inflammation and neuronal degeneration. In this study, we investigated various nitrosative modifications of bovine carbonic anhydrase II (CAII) through qualitative and semi-quantitative analysis using the combined strategy of Fourier transformation ion cyclotron resonance mass spectrometry (FT-ICR MS) and ion-trap tandem mass spectrometry (IT-MS/MS). FT-ICR MS and its spectra were used for the search of the pattern of nitrosative modifications. Identification of nitrosatively modified tyrosine sites were executed through IT-MS/MS. In addition, we also tried to infer the reason for the site-specific nitrosative modifications in CAII. In view of the above purpose, we have explored-i) the side chain accessibility, ii) the electrostatic environment originated from the acidic/basic amino acid residues neighboring to the nitrosatively modified site and iii) the existence of competing amino acid residues for nitration.

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“…Nitric oxide (NO), an important multifunctional biomolecule, exerts various cytotoxic effects including inhibition of mitochondrial function and activation of endoplasmic reticulum stress [14], and is known to be involved in a variety of diseases such as neurodegenerative disorders, arteriosclerosis, and diabetes mellitus [13,20]. For instance, endoplasmic reticulum stress triggered by NO overproduction, leads to b-cell apoptosis via CHOP induction and caspase-12 activation [29].…”

Section: Introductionmentioning

confidence: 99%

Cyclic stretch-induced apoptosis in rat annulus fibrosus cells is mediated in part by endoplasmic reticulum stress through nitric oxide production

et al. 2011

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Various mechanical stresses in vivo induce disc cell apoptosis and intervertebral disc (IVD) degeneration, but the underlying molecular mechanism is not fully known. The aim of this study was to investigate the role of endoplasmic reticulum stress in cyclic stretch-induced apoptosis of rat annulus fibrosus (AF) cells. Flexercell Tension Plus system was used to apply cyclic stretch to rat annulus fibrosus cells at a frequency of 0.5 Hz with 20% elongation for 12, 24, 36, or 48 h. Apoptosis was detected by flow cytometry, and nuclei morphologic changes were visualized by Hoechst 33258 staining and caspase-8, 9 activity assays. The expression of the markers of endoplasmic reticulum stress including CHOP, GRP78, and caspase-12 were determined by RT-PCR and Western blot. Mitochondrial membrane potential change was observed by JC-1 staining in situ. In addition, the levels of the nitric oxide (NO) were determined with the Griess reaction and fluorescence staining. The results indicated that cyclic stretch at a frequency of 0.5 Hz with 20% elongationinduced apoptosis in rat AF cells. Prolonged exposure of the unphysiologically cyclic stretch to AF cells caused NO overproduction, up-regulation of endoplasmic reticulum stress markers including CHOP, GRP78, and caspase-12, depolarization of mitochondria and activation of caspase-9. However, cyclic stretch at this level had no effect on caspase-8 activity. In addition, specific inhibitor of caspase-12 (Z-ATAD-FMK) and caspase-9 (Z-LEHD-FMK) partly suppressed cyclic stretch-induced AF cell apoptosis and the anti-apoptotic effects of the caspase inhibitors were additive. Our data suggest that endoplasmic reticulum stress, likely mediated by NO, contributes to the AF cell apoptosis induced by cyclic stretch in addition to the mitochondrial pathway. These findings could be helpful to understand the mechanism of disc cell apoptosis, the root cause of IVD degeneration.

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Role of protein tyrosine nitration in neurodegenerative diseases and atherosclerosis

Cited by 67 publications

References 75 publications

Chronic Ethanol Consumption-induced Pancreatic β-Cell Dysfunction and Apoptosis through Glucokinase Nitration and Its Down-regulation

Chronic Ethanol Consumption-induced Pancreatic β-Cell Dysfunction and Apoptosis through Glucokinase Nitration and Its Down-regulation

Mass Spectrometry Analysis of In Vitro Nitration of Carbonic Anhydrase II

Cyclic stretch-induced apoptosis in rat annulus fibrosus cells is mediated in part by endoplasmic reticulum stress through nitric oxide production

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