Protein Tyrosine Nitration: Role in Aging

Chakravarti, Bulbul; Chakravarti, Deb N.

doi:10.2174/1874609810666170315112634

Cited by 19 publications

(18 citation statements)

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“…3 D). In addition to glycation, nitration of proteins is another important non-enzymatic modification in aging [19] . In order to investigate this, iNOS and 3-NT-levels were determined by IF labeling.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, Helman and colleagues were recently able to show that an increased expression of p16 Ink4a enhances the insulin secretory capacity of β-cells in advanced age, which is in contrast to the previous literature [16] , [17] , [18] . Further well-known age-related changes include accumulation of non-enzymatic modified proteins, such as glycation (formation of advanced glycation endproducts, AGEs), oxidation or nitration of proteins [19] , [20] , [21] , [22] .…”

Section: Introductionmentioning

confidence: 99%

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Age-related oxidative changes in pancreatic islets are predominantly located in the vascular system

et al. 2018

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Aged tissues usually show a decreased regenerative capacity accompanied by a decline in functionality. During aging pancreatic islets also undergo several morphological and metabolic changes. Besides proliferative and regenerative limitations, endocrine cells lose their secretory capacity, contributing to a decline in functional islet mass and a deregulated glucose homeostasis. This is linked to several features of aging, such as induction of cellular senescence or the formation of modified proteins, such as advanced glycation end products (AGEs) - the latter mainly examined in relation to hyperglycemia and in disease models. However, age-related changes of endocrine islets under normoglycemic and non-pathologic conditions are poorly investigated. Therefore, a characterization of pancreatic tissue sections as wells as plasma samples of wild-type mice (C57BL/6J) at various age groups (2.5, 5, 10, 15, 21 months) was performed. Our findings reveal that mice at older age are able to secret sufficient amounts of insulin to maintain normoglycemia. During aging the pancreatic islet area increased and the islet size doubled in 21 months old mice when compared to 2.5 months old mice, whereas the islet number was unchanged. This was accompanied by an age-dependent decrease in Ki-67 levels and pancreatic duodenal homeobox-1 (PDX-1), indicating a decline in proliferative and regenerative capacity of pancreatic islets with advancing age. In contrast, the number of p16Ink4a-positive nuclei within the islets was elevated starting from 10 months of age. Interestingly, AGEs accumulated exclusively in the islet blood vessels of old mice associated with increased amounts of inflammatory markers, such as the inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT). In summary, the age-related increase in islet size and area was associated with the induction of senescence, accompanied by an accumulation of non-enzymatically modified proteins in the islet vascular system.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Age-related oxidative changes in pancreatic islets are predominantly located in the vascular system

et al. 2018

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“…The increased oxidative stress levels might be originated from normal metabolism of endogenous and exogenous compounds, leading to oxidative damage (Gregg et al, 2012) to cellular macromolecules such as proteins and lipids. Indeed, nitroxidative post-translational protein modifications are considered a well-established marker for oxidative stress during the aging process, which may negatively affect the functions of the modified target proteins prior to the observation of a full-blown organ damage (Abdelmegeed et al, 2013; Chakravarti and Chakravarti, 2017; Moon et al, 2008; Ortuno-Sahagun et al, 2014; Percy et al, 2005). Consistent with these reports, we found that the levels of renal H 2 O 2 , protein oxidation, and nitration, were significantly higher in aged WT compared to the aged Cyp2e1 -null mice and young mouse groups.…”

Section: Discussionmentioning

confidence: 99%

“…This theory states that the highly reactive oxidative radicals may increase damage in aged tissues by the reaction of the free radicals with cellular macromolecules, leading to alteration and/or deterioration of normal cellular functions, resulting in organ damage. Constantly, reactive oxygen species (ROS) and reactive nitrogen species (RNS) were reported to increase progressively with aging leading to the accumulation of oxidized and/or nitrated proteins in aged organs (Chakravarti and Chakravarti, 2017; Reeg and Grune, 2015). …”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450-2E1 is involved in aging-related kidney damage in mice through increased nitroxidative stress

Abdelmegeed

Choi

et al. 2017

Food and Chemical Toxicology

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The aim of this study was to investigate the role of cytochrome P450-2E1 (CYP2E1) in aging-dependent kidney damage since it is poorly understood. Young (7 weeks) and aged female (16–17 months old) wild-type (WT) and Cyp2e1-null mice were used. Kidney histology showed that aged WT mice exhibited typical signs of kidney aging such as cell vacuolation, inflammatory cell infiltration, cellular apoptosis, glomerulonephropathy, and fibrosis, along with significantly elevated levels of renal TNF-α and serum creatinine than all other groups. Furthermore, the highest levels of renal hydrogen peroxide, protein carbonylation and nitration were observed in aged WT mice. These increases in the aged WT mice were accompanied by increased levels of iNOS and mitochondrial nitroxidative stress through altered amounts and activities of the mitochondrial complex proteins and significantly reduced levels of the antioxidant glutathione (GSH). In contrast, the aged Cyp2e1-null mice exhibited significantly higher antioxidant capacity with elevated heme oxygenase-1 and catalase activities compared to all other groups, while maintaining normal GSH levels with significantly less mitochondrial nitroxidative stress compared to the aged WT mice. Thus, CYP2E1 is important in causing aging-related kidney damage most likely through increasing nitroxidative stress and that CYP2E1 could be a potential target in preventing aging-related kidney diseases.

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“…The second step in the mechanism of Tyr nitration is the formation of 3-nitrotyrosine (NO 2 Tyr, 3-NT) from the reaction between Tyr• and •NO 2 . 10,11 Under several oxidative conditions, NO 2 Tyr levels are increased by the NO-dependent Tyr nitration of proteins; it often localizes to specific tissue regions and cell types. 10 Nitric oxide (NO) is derived from L-arginine by nitric oxide synthases (NOS), catalyzing the oxidation of L-arginine to L-citrullin and NO.…”

Section: Introductionmentioning

confidence: 99%

Nitration of protein phosphatase 2A increases via Epac1/PLCε/CaMKII/HDAC5/iNOS cascade in human endometrial stromal cell decidualization

Lee

Choi

et al. 2020

The FASEB Journal

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Protein Tyrosine Nitration: Role in Aging

Cited by 19 publications

References 0 publications

Age-related oxidative changes in pancreatic islets are predominantly located in the vascular system

Age-related oxidative changes in pancreatic islets are predominantly located in the vascular system

Cytochrome P450-2E1 is involved in aging-related kidney damage in mice through increased nitroxidative stress

Nitration of protein phosphatase 2A increases via Epac1/PLCε/CaMKII/HDAC5/iNOS cascade in human endometrial stromal cell decidualization

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