DJ-1 Protects Pancreatic Beta Cells from Cytokine- and Streptozotocin-Mediated Cell Death

Jain, Deepak; Weber, Gesine; Eberhard, Daniel; Mehana, AE; Eglinger, Jan; Welters, Alena; Bartosinska, Barbara; Jeruschke, Kay; Weiß, Jürgen; Päth, G; Ariga, Hiroyoshi; Seufert, Jochen; Lammert, Eckhard

doi:10.1371/journal.pone.0138535

Cited by 21 publications

(14 citation statements)

References 42 publications

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“…It is well known that obesity is one of the most important risk factors for T2DM, and ectopic fat accumulation can induce glucose metabolism disorder and insulin resistance 18 . Previous articles also reported that DJ-1 has a moderating effect on T2DM 10 , 12 , 19 , 20 . In the present study, deletion of DJ-1 ameliorated glucose metabolism and insulin sensitivity in HFD-induced mice model.…”

Section: Discussionmentioning

confidence: 85%

DJ-1 Deficiency Protects Hepatic Steatosis by Enhancing Fatty Acid Oxidation in Mice

et al. 2018

Int. J. Biol. Sci.

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Our previous studies have shown that DJ-1 play important roles in progression of liver diseases through modulating hepatic ROS production and immune response, but its role in hepatic steatosis remains obscure. In the present study, by adopting a high-fat-diet (HFD) induced mice model, we found that DJ-1 knockout (DJ-1-/-) mice showing decreased HFD-induced obesity and visceral adipose accumulation. In line with these changes, there were also reduced liver weight and ameliorated hepatic triglyceride (TG) accumulation in DJ-1-/- mice compared to wild-type (WT) mice. And there were also decreased blood glucose levels and insulin resistance and reduced glucose metabolic disorder in DJ-1-/- mice, whereas there were no significant differences in total cholesterol (TC) and serum lipid in two groups of mice. Mechanistically, we found that there were no differences in food intake in these two genotypes of mice. Furthermore, there were no significant differences in fatty acid synthesis and glycolysis, but the expression of key enzymes in fatty acid oxidation and the tricarboxylic acid (TCA) cycle, such as Cpt1α, Pparα, Acox1, Cs, Idh1 and Idh2, was increased in DJ-1-/- mice liver, suggesting that there was enhanced fatty acids oxidation and TCA cycle in DJ-1-/- mice. Our data indicate that deletion of DJ-1 enhancing fatty acids oxidation resulting in lower hepatic TG accumulation in mice, which protecting mice hepatic steatosis.

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Section: Discussionmentioning

confidence: 85%

DJ-1 Deficiency Protects Hepatic Steatosis by Enhancing Fatty Acid Oxidation in Mice

et al. 2018

Int. J. Biol. Sci.

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“…In contrast, knockdown of DJ-1 in the cells by the small interfering RNA markedly reduced cell survival under same experimental conditions (Inberg and Linial, 2010 ). Other reports have shown that DJ-1 protein significantly protected against STZ-induced or cytokine-induced pancreatic β-cell death in DJ-1 knockout mice, leading the authors to suggest that the DJ-1 is required to protect against oxidative stress including STZ and cytokine-induced β-cell death (Inberg and Linial, 2010 ; Jain et al, 2015 ).…”

Section: Resultsmentioning

confidence: 99%

Tat-DJ-1 inhibits oxidative stress-mediated RINm5F cell death through suppression of NF-κB and MAPK activation

Kim

et al. 2016

Med Chem Res

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Oxidative stress is highly involved in the development of diabetes mellitus by destruction of pancreatic β-cells. DJ-1 is an antioxidant protein and DJ-1 expression levels are known to be reduced in diabetes mellitus. Thus, we examined the effects of DJ-1 protein against oxidative stress-induced pancreatic β-cell (RINm5F) death using cell permeable wild-type and mutant-type (C106A) Tat-DJ-1 proteins, which both efficiently transduced into RINm5F cells. Intracellular stability of wild-type Tat-DJ-1 persisted two times longer than C106A Tat-DJ-1. Wild-type Tat-DJ-1 protein markedly protected cells from hydrogen peroxide-induced toxicities such as cell death, reactive oxygen species generation, and DNA fragmentation. Further, wild-type Tat-DJ-1 protein significantly inhibited hydrogen peroxide-induced activation of mitogen-activated protein kinases and NF-κB signaling. On the other hand, C106A Tat-DJ-1 protein did not show the same protective effects. These results indicate that wild-type Tat-DJ-1 inhibits oxidative stress-induced cellular toxicity and activation of mitogen-activated protein kinases and NF-κB signals in RINm5F cells. These results suggest that wild-type Tat-DJ-1 protein may be a potential therapeutic agent against diabetes mellitus or toward the prevention of pancreatic β-cell destruction.

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“…Similarly, other studies have shown that DJ-1 protects against pancreatic β-cell death in STZ-exposed mice. In DJ-1 KO mice, insulin levels are significantly lower compared to those in STZ-treated mice ( 27 ). Other studies have shown that high glucose levels and FFA affect β-cell functionality and survival throughout the course of DM.…”

Section: Resultsmentioning

confidence: 99%

Protective effects of Tat-DJ-1 protein against streptozotocin-induced diabetes in a mice model

Yeo

Shin

et al. 2018

BMB Rep.

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A major feature of type 1 diabetes mellitus (T1DM) is hyperglycemia and dysfunction of pancreatic β-cells. In a previous study, we have shown that Tat-DJ-1 protein inhibits pancreatic RINm5F β-cell death caused by oxidative stress. In this study, we examined effects of Tat-DJ-1 protein on streptozotocin (STZ)-induced diabetic mice. Wild type (WT) Tat-DJ-1 protein transduced into pancreas where it markedly inhibited pancreatic β-cell destruction and regulated levels of serum parameters including insulin, alkaline phosphatase (ALP), and free fatty acid (FFA) secretion. In addition, transduced WT Tat-DJ-1 protein significantly inhibited the activation of NF-κB and MAPK (ERK and p38) expression as well as expression of COX-2 and iNOS in STZ exposed pancreas. In contrast, treatment with C106A mutant Tat-DJ-1 protein showed no protective effects. Collectively, our results indicate that WT Tat-DJ-1 protein can significantly ameliorate pancreatic tissues in STZ-induced diabetes in mice.

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DJ-1 Protects Pancreatic Beta Cells from Cytokine- and Streptozotocin-Mediated Cell Death

Cited by 21 publications

References 42 publications

DJ-1 Deficiency Protects Hepatic Steatosis by Enhancing Fatty Acid Oxidation in Mice

DJ-1 Deficiency Protects Hepatic Steatosis by Enhancing Fatty Acid Oxidation in Mice

Tat-DJ-1 inhibits oxidative stress-mediated RINm5F cell death through suppression of NF-κB and MAPK activation

Protective effects of Tat-DJ-1 protein against streptozotocin-induced diabetes in a mice model

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