Involvement of protein kinase C delta in the alteration of mitochondrial mass in human cells under oxidative stress.
Alteration of mitochondrial mass of human 143B osteosarcoma cells upon exposure to hydrogen peroxide (H(2)O(2)) was investigated. We found that mitochondrial mass and the intracellular level of H(2)O(2) were increased by exogenous H(2)O(2), which was accompanied with up-regulation of functional PKCdelta. To investigate the role of PKCdelta in H(2)O(2)-induced increase of mitochondrial mass, we treated 143B cells with PKCdelta activator, bistratene A, and PKCdelta inhibitor, rottlerin, respectively. The results show that bistratene A caused an increase of mitochondrial mass and that the H(2)O(2)-induced increase of mitochondrial mass was completely suppressed by rottlerin. Furthermore, we found that activation of PKCdelta by bistratene A increased the intracellular levels of H(2)O(2) and MnSOD protein expression. By contrast, suppression of PKCdelta by rottlerin decreased the intracellular levels of H(2)O(2) and MnSOD protein expression. Moreover, we noted that MnSOD expression was highly correlated with the expression of p53, which was controlled by PKCdelta. Finally, we demonstrated that PKCdelta was overexpressed in skin fibroblasts of patients with MERRF syndrome. Taken together, we conclude that PKCdelta is involved in the regulation of mitochondrial mass and intracellular H(2)O(2) in human cells and may play a key role in the overproliferation of mitochondria in the affected tissues of patients with mitochondrial diseases such as MERRF syndrome.
Lee
Cheng-Feng
CF
Department of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
Chen
Yin-Chiu
YC
Liu
Chun-Yi
CY
Wei
Yau-Huei
YH
D000081:Acetamides / Q000494:pharmacology; D000098:Acetophenones / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D017243:MERRF Syndrome / Q000201:enzymology*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D018384:Oxidative Stress; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D011714:Pyrans / Q000494:pharmacology; D012867:Skin / Q000201:enzymology / Q000473:pathology; D013141:Spiro Compounds / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
D000081:Acetamides; D000098:Acetophenones; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D011714:Pyrans; D013141:Spiro Compounds; D016159:Tumor Suppressor Protein p53; C059975:bistratene A; D006861:Hydrogen Peroxide; C085746:rottlerin; D013482:Superoxide Dismutase; D051745:Protein Kinase C-delta