Oxidative post-translational modifications and their involvement in the pathogenesis of autoimmune diseases

Ryan, Brent J.; Nissim, Ahuva; Winyard, Paul G.

doi:10.1016/j.redox.2014.05.004

Cited by 97 publications

(59 citation statements)

References 105 publications

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“…High levels of ROS may lead to oxidative post-translational modification (oxPTM) of beta cell self-proteins and the formation of neoepitopes. Neoepitopes are epitopes that have not been previously presented to the immune system [3,4] and therefore escape immune tolerance and generate autoimmunity. Other intracellular events, such as increases in ROS and endoplasmic reticulum stress, impair beta cell autophagic activity [5].…”

Section: Introductionmentioning

confidence: 99%

Antibodies to post-translationally modified insulin in type 1 diabetes

et al. 2015

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Aim/hypothesis Insulin is the most specific beta cell antigen and a potential primary autoantigen in type 1 diabetes. Insulin autoantibodies (IAAs) are the earliest marker of beta cell autoimmunity; however, only slightly more than 50% of children and even fewer adults newly diagnosed with type 1 diabetes are IAA positive. The aim of this investigation was to determine if oxidative post-translational modification (oxPTM) of insulin by reactive oxidants associated with islet inflammation generates neoepitopes that stimulate an immune response in individuals with type 1 diabetes. Methods oxPTM of insulin was generated using ribose and various reactive oxygen species. Modifications were analysed by SDS-PAGE, three-dimensional fluorescence and MS. Autoreactivity to oxPTM insulin (oxPTM-INS) was observed by ELISA and western blotting, using sera from participants with type 1 or type 2 diabetes and healthy controls as probes. IAAwas measured using the gold-standard radiobinding assay (RBA). Results MS of oxPTM-INS identified chlorination of Tyr16 and Tyr26; oxidation of His5, Cys7 and Phe24; a nd g l y c at i o n of Lys 2 9 a n d P h e 1 i n ch a i n B . Significantly higher binding to oxPTM-INS vs native insulin was observed in participants with type 1 diabetes, with 84% sensitivity compared with 61% sensitivity for RBA. oxPTM-INS autoantibodies and IAA co-existed in 50% of those with type 1 diabetes. Importantly 34% of those with diabetes who were IAA negative were oxPTM-INS positive. Altogether, 95% of participants with type 1 diabetes presented with autoimmunity to insulin by RBA, oxPTM-INS or both. Binding to oxPTM-INS was directed towards oxPTM-INS fragments with slower mobility than native insulin.

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Section: Introductionmentioning

confidence: 99%

Antibodies to post-translationally modified insulin in type 1 diabetes

et al. 2015

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“…4-HNE can bind to cysteine, histidine, and lysine residues of proteins via Michael addition reaction (Bennaars-Eiden et al, 2002;Macpherson et al, 2007). Thus, 4-HNE can increase oxidative post translational modification (PTM) and then alter protein function and cell signaling (Jin and Zangar, 2009;Ryan et al, 2014). 4-HNE could inhibit PTEN (Phosphatase and tensin homolog) activity in the hepatocytes (Shearn et al, 2011;Ayala et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

4-Hydroxynonenal Promotes Growth and Angiogenesis of Breast Cancer Cells through HIF-1α Stabilization

Li¹,

Tian²,

Shi³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Abstract4-Hydroxynonenal (4-HNE) is a stable end product of lipid peroxidation, which has been shown to play an important role in cell signal transduction, while increasing cell growth and differentiation. 4-HNE could inhibit phosphatase and tensin homolog (PTEN) activity in hepatocytes and increased levels have been found in human invasive breast cancer. Here we report that 4-HNE increased the cell growth of breast cancer cells as revealed by colony formation assay. Moreover, vascular endothelial growth factor (VEGF) expression was elevated, while protein levels of hypoxia inducible factor 1 alpha (HIF-1α) were up-regulated. Sirtuin-3 (SIRT3), a major mitochondria NAD+-dependent deacetylase, is reported to destabilize HIF-1α. Here, 4-HNE could inhibit the deacetylase activity of SIRT3 by thiol-specific modification. We further demonstrated that the regulation by 4-HNE of levels of HIF-1α and VEGF depends on SIRT3. Consistent with this, 4-HNE could not increase the cell growth in SIRT3 knockdown breast cancer cells. Additionally, 4-HNE promoted angiogenesis and invasion of breast cancer cells in a SIRT3-dependent manner. In conclusion, we propose that 4-HNE promotes growth, invasion and angiogenesis of breast cancer cells through the SIRT3-HIF-1α-VEGF axis.

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“…Another endogenous resource of ROS is inflammatory reaction, such as release of ROS by polymorpho-nuclear leukocytes and macrophage peroxisomes. Exogenous sources of ROS include smoke, air pollution, and pesticides [3,4]. ROS has important roles in the body, including its involvement in the signal transduction of inflammation to resist pathogen infection [5].…”

Section: Introductionmentioning

confidence: 99%

Determination of Antioxidant Activity in Garlic (<i>Allium sativum</i>) Extracts Subjected to Boiling Process <i>in vitro</i>

Liu¹,

Yang²,

Yao³

et al. 2014

JFNR

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Garlic is a vegetable known to be a good antioxidant food resource around the world. Several studies on the antioxidant activity of garlic, mainly conducted using one or two methods, have been reported. However, comparison of the antioxidant activity of garlic before and after cooking is rarely reported. In this study, we compared the antioxidant activity of garlic aqueous and methanol extracts processed before and after boiling to mimic the cooking process. By testing the antioxidant activities of the extracts in different chemical mimic systems in vitro, namely, ABTS [2, 2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid)] and DPPH (2, 2-diphenyl-1-picrylhydrazyl) radical scavenging activities, reducing power, and metal chelating ability, we found the following data: (1) no significant difference was observed on the ABTS radical scavenging activities of garlic aqueous and methanol extracts before and after boiling process; (2) the reducing power of garlic aqueous and methanol extracts decreased by 25.9% and 14.1%, respectively, whereas the metal chelating activity of boiled garlic aqueous extracts increased by 54.7%; and (3) DPPH radical scavenging test may not be suitable to examine the garlic extracts. In addition, the ABTS radical scavenging activities of garlic extracts were very stable at pH ranges similar in human bodies, and both sulfhydryl and phenolic compounds were probably responsible for the antioxidant ability of garlic. The boiling process destroyed only a small part of garlic bio-ingredients related to antioxidant activity properties.

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Oxidative post-translational modifications and their involvement in the pathogenesis of autoimmune diseases

Cited by 97 publications

References 105 publications

Antibodies to post-translationally modified insulin in type 1 diabetes

Antibodies to post-translationally modified insulin in type 1 diabetes

4-Hydroxynonenal Promotes Growth and Angiogenesis of Breast Cancer Cells through HIF-1α Stabilization

Determination of Antioxidant Activity in Garlic (<i>Allium sativum</i>) Extracts Subjected to Boiling Process <i>in vitro</i>

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