Pro-oxidant/antioxidant balance controls pancreatic β-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 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, decreasing ROS production in vivo reduced β-cell differentiation. Moreover, in cultures of pancreatic explants, progenitors were highly sensitive to ROS stimulation and responded by generating β-cells. ROS enhanced β-cell differentiation through modulation of ERK1/2 signaling. Gene transfer and pharmacological manipulations, which diminish cellular ROS levels, also interfered with normal β-cell differentiation. This study highlights the role of the redox balance on β-cell development and provides information that will be useful for improving β-cell production from embryonic stem cells, a step in cell therapy for diabetes.

Embryonic exposures to perfluorooctanesulfonic acid (PFOS) disrupt pancreatic organogenesis in the zebrafish, Danio rerio

“…It is possible that this increase of pdx1 expression causes the attenuation of islet effects at the highest PFOS concentration for all of the islet morphology and gene expression data, and future study of causality is necessary. The mechanism by which pdx1 is induced by PFOS exposure warrants further research, though it has been shown to be sensitive to oxidative stress (Harmon et al, 2005; Hoarau et al, 2014; Kaneto et al, 1999). PFOS has been repeatedly demonstrated to induce oxidative stress across a variety of tissues and model organisms, including the zebrafish embryo (Chen et al, 2012; Hu et al, 2005; Liu et al, 2007; Shi and Zhou, 2010).…”

1,4-Naphthoquinone, a pro-oxidant, ameliorated radiation induced gastro-intestinal injury through perturbation of cellular redox and activation of Nrf2 pathway

“…Since NQ is a known pro-oxidant, it perturbs the cellular redox status of the INT 407 cells by increasing the basal level of ROS and depleting GSH/GSSG (Figure 2). Higher redox potential and electrophilic nature of quinones imparts high affinity for cellular nucleophiles like thiols of cysteine group present in proteins and glutathione contributing to its biological activity (41). Perturbation in cellular redox status is known to activate redox sensitive prosurvival transcription factor Nrf2 and its dependent cytoprotective genes (42)(43)(44)(45).…”

Therapeutic effects of Crocin in autoimmune diseases: A review

“…In diabetes, the free radicals cause damage to many organic substrates such as proteins, carbohydrates, nucleic acids, and lipids of the host cells resulting in various diabetes complications. ROS affects the β‐cells as a result of activating the transcription factor NF‐κβ in the macrophages …”

“…ROS affects the β-cells as a result of activating the transcription factor NF-κβ in the macrophages. 57 Altinoz et al demonstrated the impact of Crocin in the management of cardiovascular complications by reducing oxidative stress in diabetic rats. Crocin reduced MDA and significantly increased GSH levels in both cardiac tissues and in serum.…”