Fanconi anemia complementation group C protection against oxidative stress‑induced β‑cell apoptosis

Kulanuwat,Sirikul; Jungtrakoon,Prapaporn; Tangjittipokin,Watip; Yenchitsomanus,Pa‑Thai; Plengvidhya,Nattachet

doi:10.3892/mmr.2018.9163

Fanconi anemia complementation group C protection against oxidative stress‑induced β‑cell apoptosis

Authors:
- Sirikul Kulanuwat
- Prapaporn Jungtrakoon
- Watip Tangjittipokin
- Pa‑Thai Yenchitsomanus
- Nattachet Plengvidhya
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Affiliations: Siriraj Center of Research Excellence for Diabetes and Obesity, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Published online on: June 14, 2018 https://doi.org/10.3892/mmr.2018.9163
Pages: 2485-2491

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Abstract

Diabetes mellitus (DM) and other glucose metabolism abnormalities are commonly observed in individuals with Fanconi anemia (FA). FA causes an impaired response to DNA damage due to genetic defects in a cluster of genes encoded proteins involved in DNA repair. However, the mechanism by which FA is associated with DM has not been clearly elucidated. Fanconi anemia complementation group C (FANCC) is a component of FA nuclear clusters. Evidence suggests that cytoplasmic FANCC has a role in protection against oxidative stress‑induced apoptosis. As oxidative stress‑mediated β‑cell dysfunction is one of the contributors to DM pathogenesis, the present study aimed to investigate the role of FANCC in pancreatic β‑cell response to oxidative stress. Small interfering RNA‑mediated FANCC suppression caused a loss of protection against oxidative stress‑induced apoptosis, and that overexpression of FANCC reduced this effect in the human 1.1B4 β‑cell line. These findings were confirmed by Annexin V‑FITC/PI staining, caspase 3/7 activity assay, and expression levels of anti‑apoptotic and pro‑apoptotic genes. Insulin and glucokinase mRNA expression were also decreased in FANCC‑depleted 1.1B4 cells. The present study demonstrated the role of FANCC in protection against oxidative stress‑induced β‑cell apoptosis and established another mechanism that associates FANCC deficiency with β‑cell dysfunction. The finding that FANCC overexpression reduced β‑cell apoptosis advances the potential for an alternative approach to the treatment of DM caused by FANCC defects.

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