Involvement of DNA-dependent protein kinase in regulation of the mitochondrial heat shock proteins

Um, Jee Hyun; Kang, Chi Dug; Hwang, Byung Wook; Ha, Mee Young; Hur, Joong Gu; Kim, Dong Wan; Chung, Byung Seon; Kim, Sun Hee

doi:10.1016/S0145-2126(02)00264-3

« Previous Next »Leukemia Research
Volume 27, Issue 6 , Pages 509-516, June 2003

Involvement of DNA-dependent protein kinase in regulation of the mitochondrial heat shock proteins

Jee Hyun Um
- Department of Biochemistry, College of Medicine, Pusan National University, Pusan 602-739, South Korea
- Research Center for Molecular Medicine, College of Medicine, Pusan National University, Pusan 602-739, South Korea
- These authors contributed equally to this work.
Chi Dug Kang
- Department of Biochemistry, College of Medicine, Pusan National University, Pusan 602-739, South Korea
- Research Center for Molecular Medicine, College of Medicine, Pusan National University, Pusan 602-739, South Korea
- These authors contributed equally to this work.
Byung Wook Hwang
- Department of Biochemistry, College of Medicine, Pusan National University, Pusan 602-739, South Korea
Mee Young Ha
- Department of Biochemistry, College of Medicine, Pusan National University, Pusan 602-739, South Korea
Joong Gu Hur
- Department of Biochemistry, College of Medicine, Pusan National University, Pusan 602-739, South Korea
Dong Wan Kim
- Department of microbiology, College of Natural Sciences, Chang Won National University, Chang Won 641-773, South Korea
Byung Seon Chung
- Department of Biochemistry, College of Medicine, Pusan National University, Pusan 602-739, South Korea
Sun Hee Kim
- Department of Biochemistry, College of Medicine, Pusan National University, Pusan 602-739, South Korea
- Corresponding author. Fax: +82-51-248-1118.

Received 25 June 2002; accepted 10 October 2002.

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.

Keywords: Mitochondrial heat shock, Mitochondrial heat shock protein, Multidrug-resistant, Anti-apoptotic function