Proceedings of the Japan Academy, Series B
Online ISSN : 1349-2896
Print ISSN : 0386-2208
ISSN-L : 0386-2208
Original Articles
CXCL12 protects pancreatic β-cells from oxidative stress by a Nrf2-induced increase in catalase expression and activity
Svetlana DINIĆNevena GRDOVIĆAleksandra USKOKOVIĆMiloš ĐORĐEVIĆMirjana MIHAILOVIĆJelena Arambašić JOVANOVIĆGoran POZNANOVIĆMelita VIDAKOVIĆ
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2016 Volume 92 Issue 9 Pages 436-454

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Abstract

Due to intrinsically low levels of antioxidant enzyme expression and activity, insulin producing pancreatic β-cells are particularly susceptible to free radical attack. In diabetes mellitus, which is accompanied by high levels of oxidative stress, this feature of β-cells significantly contributes to their damage and dysfunction. In light of the documented pro-survival effect of chemokine C-X-C Ligand 12 (CXCL12) on pancreatic β-cells, we examined its potential role in antioxidant protection. We report that CXCL12 overexpression enhanced the resistance of rat insulinoma (Rin-5F) and primary pancreatic islet cells to hydrogen peroxide (H2O2). CXCL12 lowered the levels of DNA damage and lipid peroxidation and preserved insulin expression. This effect was mediated through an increase in catalase (CAT) activity. By activating downstream p38, Akt and ERK kinases, CXCL12 facilitated Nrf2 nuclear translocation and enhanced its binding to the CAT gene promoter, inducing constitutive CAT expression and activity that was essential for protecting β-cells from H2O2.

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© 2016 The Japan Academy
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