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Pro-oxidant/antioxidant balance controls pancreatic ?-cell differentiation through the ERK1/2 pathway.

ABSTRACT: During embryogenesis, the intrauterine milieu affects cell proliferation, differentiation, and function by modifying gene expression in susceptible cells, such as the pancreatic ?-cells. In this limited energy environment, mitochondrial dysfunction can lead to overproduction of reactive oxygen species (ROS) and to a decline in ?-cell function. In opposition to this toxicity, ROS are also required for insulin secretion. Here we investigated the role of ROS in ?-cell development. Surprisingly, decreasing ROS production in vivo reduced ?-cell differentiation. Moreover, in cultures of pancreatic explants, progenitors were highly sensitive to ROS stimulation and responded by generating ?-cells. ROS enhanced ?-cell differentiation through modulation of ERK1/2 signaling. Gene transfer and pharmacological manipulations, which diminish cellular ROS levels, also interfered with normal ?-cell differentiation. This study highlights the role of the redox balance on ?-cell development and provides information that will be useful for improving ?-cell production from embryonic stem cells, a step in cell therapy for diabetes.

SUBMITTER: Hoarau E

PROVIDER: S-EPMC4237262 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway.

Hoarau E E Chandra V V Rustin P P Scharfmann R R Duvillie B B

Cell death & disease 20141023

During embryogenesis, the intrauterine milieu affects cell proliferation, differentiation, and function by modifying gene expression in susceptible cells, such as the pancreatic β-cells. In this limited energy environment, mitochondrial dysfunction can lead to overproduction of reactive oxygen species (ROS) and to a decline in β-cell function. In opposition to this toxicity, ROS are also required for insulin secretion. Here we investigated the role of ROS in β-cell development. Surprisingly, dec ...[more]

PMID: 25341041

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Project description:In some countries, anabolic-androgenic steroid abuse is rampant among adolescent boys and young men, including some of those seeking physical fitness and/or pleasing appearance through various exercise types. This tactic carries the risk of severe harmful health effects, including liver injury. Most anabolic-androgenic steroid stacking protocols employed are based on the use of the 'prototypic' anabolic-androgenic steroid testosterone and/or its esters. There is a vast body of data on the effects of anabolic-androgenic steroids' abuse combined with physical exercise training on the liver antioxidant barrier in adult subjects, whereas those concerning adolescents are scant. This study aimed to assess, in adolescent male Wistar rats undergoing a 6-week moderate-intensity endurance training (treadmill running), the influence of concurrent weekly supplementation with intramuscular testosterone enanthate (TE, 8 or 80 mg/kg body weight/week) on selected indices of liver status and oxidative stress. The rats were sacrificed, and their livers and blood samples were harvested two days after the last training session. High-dose TE treatment significantly reduced body and liver weight gains. Neither low-dose nor high-dose TE treatment affected liver α-tocopherol or γ-tocopherol content, whereas low-dose TE treatment significantly lowered hepatic reduced glutathione content. TE treatment significantly elevated liver thiobarbituric acid-reactive substances content and blood activities of alkaline phosphatase and γ-glutamyltransferase, but not of aspartate aminotransferase or alanine aminotransferase. Liver catalase activity was lowered by >50% in both TE-treated groups, while superoxide dismutase activity was significantly but slightly affected (-15%) only by the high-dose TE treatment. Glutathione peroxidase and glutathione reductase activities were not significantly altered. TE treatment significantly increased liver thiobarbituric acid-reactive substances content and lowered blood HDL-cholesterol, but did not significantly affect LDL-cholesterol or triglycerides level. In conclusion, high-dose TE treatment significantly disturbed liver antioxidant barrier and prooxidative-antioxidative balance and hence counteracted favorable effects of concurrent moderate-intensity endurance training in adolescent male rats.

Dataset Information

Pro-oxidant/antioxidant balance controls pancreatic ?-cell differentiation through the ERK1/2 pathway.

Publications

Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway.

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