tailieunhanh - Báo cáo khoa học: DNA-dependent protein kinase is involved in heat shock protein-mediated accumulation of hypoxia-inducible factor-1a in hypoxic preconditioned HepG2 cells

Hypoxic preconditioning may afford protection against subsequent lethal hypoxia. As hypoxic tolerance induces changes in the expression of genes involved in DNA damage and repair response pathways, we investigated whether DNA-dependent protein kinase (DNA-PK), one of the DNA dou-ble-strand break repair proteins, could be involved in hypoxic precondi-tioning-induced protective signaling cascades. | DNA-dependent protein kinase is involved in heat shock protein-mediated accumulation of hypoxia-inducible factor-1 a in hypoxic preconditioned HepG2 cells Moon Jung Kang1 Sun Min Jung2 Mi Ju Kim1 2 Jae Ho Bae1 2 Hak Bong Kim1 2 Joo Young Kim1 2 Soo Jung Park1 Hye Soon Song2 Dong Wan Kim3 Chi Dug Kang1 and Sun Hee Kim1 2 1 Department of Biochemistry Pusan National university Schoolof Medicine Busan South Korea 2 Research Center for Ischemic Tissue regeneration Pusan NationalUniversity Schoolof Medicine Busan South Korea 3 Department of Microbiology College of NaturalSciences Chang Won NationalUniversity South Korea Keywords DNA-PK heat shock protein HIF-1a HSF1 hypoxic preconditioning Correspondence S. H. Kim and C. D. Kang Department of Biochemistry Pusan NationalUniversity Schoolof Medicine Busan 602-739 South Korea Fax 82 51 248 1118 Tel 82 51 240 7738 9 E-mail ksh7738@ kcdshbw@ Received 14 August 2008 revised 30 September 2008 accepted 3 October 2008 doi Hypoxic preconditioning may afford protection against subsequent lethal hypoxia. As hypoxic tolerance induces changes in the expression of genes involved in DNA damage and repair response pathways we investigated whether DNA-dependent protein kinase DNA-PK one of the DNA double-strand break repair proteins could be involved in hypoxic preconditioning-induced protective signaling cascades. We showed that induction of hypoxia-inducible factor-1a expression during hypoxic preconditioning by repeated hypoxic exposure was associated with increased mRNA and protein levels of DNA-PK catalytic subunit DNA-PKcs and Ku70 Ku80 the DNA-PK components in human hepatoma HepG2 cells followed by upregulation of Hsp70 Hsp90 and Bcl-2 and concurrent downregulation of Bax. Additionally loss of DNA-PKcs led to attenuated expression of Hsp70 Hsp90. accelerated hypoxia-inducible factor-1a degradation and increased susceptibility to hypoxia-induced cell death. We also found that .