title: Involvement of DNA-dependent protein kinase in regulation of the mitochondrial heat shock proteins.
abstract: Since DNA-dependent protein kinase (DNA-PK) has been known to play a protective role against drug-induced apoptosis, the role of DNA-PK in the regulation of mitochondrial heat shock proteins by anticancer drugs was examined. The levels of basal and drug-induced mitochondrial heat shock proteins of drug-sensitive parental cells were higher than those of multidrug-resistant (MDR) cells. We also demonstrated that the development of MDR might be correlated with the increased expression of Ku-subunit of DNA-PK and concurrent down-regulation of mitochondrial heat shock proteins. The basal mtHsp70 and Hsp60 levels of Ku70(-/-) cells, which were known to be sensitive to anticancer drugs, were higher than those of parental MEF cells, but conversely these mitochondrial heat shock proteins of R7080-6 cells over-expressing both Ku70 and Ku80 were lower than those of parental Rat-1 cells. Also, the mtHsp70 and Hsp60 levels of DNA-PKcs-deficient SCID cells were higher than those of parental CB-17 cells. Our results suggest the possibility that mitochondrial heat shock protein may be one of determinants of drug sensitivity and could be regulated by DNA-PK activity.
authors.affiliation: Department of Biochemistry, College of Medicine, Pusan National University, Pusan 602-739, South Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Um
authors.forename: Chi Dug
authors.initials: CD
authors.lastname: Kang
authors.forename: Byung Wook
authors.initials: BW
authors.lastname: Hwang
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Ha
authors.forename: Joong Gu
authors.initials: JG
authors.lastname: Hur
authors.forename: Dong Wan
authors.initials: DW
authors.lastname: Kim
authors.forename: Byung Seon
authors.initials: BS
authors.lastname: Chung
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D018834:Chaperonin 60 / Q000378:metabolism*; D004265:DNA Helicases; D004260:DNA Repair / Q000187:drug effects; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D018432:Drug Resistance, Multiple; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D000072200:Ku Autoantigen; D007938:Leukemia / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats
chemical_list: D034961:Antigens, Nuclear; D000970:Antineoplastic Agents; D018834:Chaperonin 60; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; C000606511:Xrcc6 protein, rat; D000072200:Ku Autoantigen