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Autophagy induction plays a protective role against hypoxic stress in human dental pulp cells
Author(s) -
Park SamYoung,
Sun EunGene,
Lee Yeonju,
Kim MinSeok,
Kim JaeHyung,
Kim WonJae,
Jung JiYeon
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26360
Subject(s) - autophagy , pi3k/akt/mtor pathway , chemistry , apoptosis , microbiology and biotechnology , cytochrome c , downregulation and upregulation , caspase 3 , poly adp ribose polymerase , viability assay , programmed cell death , biochemistry , biology , dna , polymerase , gene
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 (CoCl 2 ) treated HDPCs, to mimic hypoxic conditions, decreased cell viability. Also, apoptosis‐related signal molecules, cleaved caspase‐3 and PARP levels, were enhanced in CoCl 2 ‐treated HDPCs. HDPCs exposed to CoCl 2 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 CoCl 2 ‐treated HDPCs. However, autophagy activation by rapamycin enhanced the p62 and LC3‐II levels, whereas it reduced PARP and caspase‐3 cleavage induced by CoCl 2. These results revealed that CoCl 2 ‐activated autophagy showed survival effects against CoCl 2 ‐induced apoptosis in the HDPCs. CoCl 2 upregulated HIF‐1α and decreased the phosphorylation of mTOR/p70S6K. HIF‐1α inhibitor, YC‐1 decreased p62 and LC3‐II levels, whereas it augmented PARP and caspase‐3 cleavage in response to CoCl 2 . Also, YC‐1 enhanced the phosphorylation of mTOR and p70S6K suppressed by CoCl 2 , demonstrating that CoCl 2 ‐induced autophagy via mTOR/p70S6K is mediated by HIF‐1α. Taken together, these finding suggest that CoCl 2 ‐induced autophagy mediated by the mTOR/p70S6K pathway plays a protective role against hypoxic stress in HDPCs.