Autophagy induction plays a protective role against hypoxic stress in human dental pulp cells

作者：Park Sam Young; Sun Eun Gene; Lee Yeonju; Kim Min Seok; Kim Jae Hyung; Kim Won Jae^*; Jung Ji Yeon^*

来源：Journal of Cellular Biochemistry, 2018, 119(2): 1992-2002.

DOI：10.1002/jcb.26360

• apoptosis
• autophagy
• cobalt chloride
• human dental pulp cells
• hypoxia

Human dental pulp exposed to hypoxic conditions induces cell death accompanied by autophagy. However, the role of hypoxia-induced autophagy in human dental pulp cells (HDPCs) is unclear. The present study aimed to investigate the role of autophagy in hypoxia-induced apoptosis of HDPCs. Cobalt chloride (CoCl2) treated HDPCs, to mimic hypoxic conditions, decreased cell viability. Also, apoptosis-related signal molecules, cleaved caspase-3 and PARP levels, were enhanced in CoCl2-treated HDPCs. HDPCs exposed to CoCl2 also promoted autophagy, showing upregulated p62 and microtubule-associated protein 1 light chain 3 (LC3)-II levels, typical autophagic markers, and increased acidic autophagolysosomal vacuoles. Autophagy inhibition by 3 methyladenine (3MA) or RNA interference of LC3B resulted in increased levels of cleaved PARP and caspase-3, and the release of cytochrome c from mitochondria into cytosol in the CoCl2-treated HDPCs. However, autophagy activation by rapamycin enhanced the p62 and LC3-II levels, whereas it reduced PARP and caspase-3 cleavage induced by CoCl2. These results revealed that CoCl2-activated autophagy showed survival effects against CoCl2-induced apoptosis in the HDPCs. CoCl2 upregulated HIF-1 and decreased the phosphorylation of mTOR/p70S6K. HIF-1 inhibitor, YC-1 decreased p62 and LC3-II levels, whereas it augmented PARP and caspase-3 cleavage in response to CoCl2. Also, YC-1 enhanced the phosphorylation of mTOR and p70S6K suppressed by CoCl2, demonstrating that CoCl2-induced autophagy via mTOR/p70S6K is mediated by HIF-1. Taken together, these finding suggest that CoCl2-induced autophagy mediated by the mTOR/p70S6K pathway plays a protective role against hypoxic stress in HDPCs.

• 出版日期2018-2