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1,25‐(OH)2D3 protects Schwann cells against advanced glycation end products‐induced apoptosis through PKA‐NF‐&kgr;B pathway

Shiqing Xu,Jing Li,M. Zhai,Xiaoqin Yao,Hong-lin Liu,Tingting Deng,Hanqing Cai,Wanru Zhang,Wenjian Zhang,J. Lou,Liang Peng

Published 2019 in Life Science

ABSTRACT

Aims To explore the effect and mechanism of 1, 25‐(OH)2D3 on Schwann cell apoptosis induced by advanced glycation end products. Main methods Schwann cells, isolated from rodent sciatic nerve were incubated with AGE‐modified bovine serum albumin(AGE) to mimic diabetic conditions and 1,25‐(OH)2D3 was used as protector. Cell apoptosis was detected by PI/Annexin‐V staining, caspase 3 activity assay and western blotting for caspase 3 and PARP. The activation of protein kinase A (PKA) and nuclear factor kappa‐B (NF‐&kgr;B) was evaluated by western blot. Immunofluorescent staining was used for intercellular location of NF‐&kgr;B. Cytokine secretion was evaluated by enzyme‐linked immunosorbent assay. Key findings Schwann cell apoptosis accelerated after incubating with AGE. However, if combining 1,25‐(OH)2D3 with AGE, apoptosis decreased significantly. 1,25‐(OH)2D3 enhanced PKA activity, but inhibited AGE‐induced nuclear translocation of NF‐&kgr;B. Furthermore, PKA activator (8‐bromoadenoside cyclic adenoside monophosphate, 8‐Br‐cAMP) or NF‐&kgr;B inhibitor (caffeic acid phenethyl ester, CAPE) could reduce the apoptosis, decreased cleaved caspase 3 and cleaved PARP, suggesting the involvement of PKA and NF‐&kgr;B pathways in the protection of 1,25‐(OH)2D3 on Schwann cells. Moreover, 8‐Br‐cAMP and CAPE could inhibit AGE‐induced secretion of interleukin(IL)‐1&bgr;, prostaglandin E2(PEG2) and cyclooxygenase 2(COX2). Interestingly, 8‐Br‐cAMP decreased phospho‐NF‐&kgr;B and inhibited nucleus translocation of NF‐&kgr;B. It hinted at the regulation of PKA to NF‐&kgr;B. Finally, a pre‐treatment of H‐89 (an inhibitor of PKA) could block the protection of 1,25‐(OH)2D3 on cell apoptosis. In conclusion, 1,25‐(OH)2D3 could protect Schwann cell against AGE‐induced apoptosis through PKA/NF‐&kgr;B pathway. Significance These findings provide experimental rationales for using vitamin D for diabetic neuropathy.

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