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Oxidative Stress‐Induced Depolymerization of Microtubules and Alteration of Mitochondrial Mass in Human Cells
Author(s) -
LEE CHENGFENG,
LIU CHUNYI,
HSIEH RONGHONG,
WEI YAUHUEI
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1338.027
Subject(s) - mitochondrion , mitochondrial dna , oxidative stress , microtubule , microbiology and biotechnology , oxidative phosphorylation , tubulin , chemistry , biology , mitochondrial biogenesis , biochemistry , gene
A bstract : Mitochondrial biogenesis is a biological process that has been intensively studied over the past few years. However, the detailed molecular mechanism underlying this increase in mitochondria remains unclear. To investigate the mechanism of such a mitochondrial proliferation, we examined alterations in mitochondria of human osteosarcoma 143B cells that had been treated with 100 to 500 μM hydrogen peroxide (H 2 O 2 ) for 48 h. The results showed that mitochondrial mass of the cell was increased with the increase of the concentration of H 2 O 2 . On the other hand, by using real‐time PCR techniques, we observed the changes of mitochondrial DNA (mtDNA) content in the cells exposed to oxidative stress. The copy number of mtDNA was increased by treatment with a low dose of H 2 O 2 but was drastically decreased after treatment with H 2 O 2 higher than 300 μM. Transmission electron microscopic images revealed that mitochondria were abnormally proliferated in cells exposed to oxidative stress. Moreover, we found that the percentage of 143B cells arrested at the G 2 /M phase increased upon treatment with H 2 O 2 . Immunostaining and microtubule fractionation assay revealed that microtubules were depolymerized in the cells that had been treated with H 2 O 2 . To understand the effect of microtubules depolymerization on the mitochondrial mass, we treated the cells with several kinds of microtubule‐active drugs, which arrest cultured cells at the G 2 /M phase. The results showed that mitochondrial mass and mtDNA copy number all were increased after such treatments. Taking these findings together, we suggest that oxidative stress‐induced microtubule derangement is one of the molecular events involved in the increase of mitochondrial mass upon treatment of human cells with H 2 O 2 .