Long-term cadmium exposure accelerates age-related mitochondrial changes in renal epithelial cells.
Long-term cadmium exposure leads to mitochondrial dysfunction in the proximal tubular epithelial cells. Mitochondrial DNA deletion may contribute to the pathogenesis of cadmium-induced nephropathy. The aim of our study is to clarify the accumulation of mitochondrial DNA deletion and mitochondrial dysfunction in the renal cortex of rats injected three times/week with 1 ml of 1 mM CdCl2 or saline for 80 weeks. After 40-week cadmium injection, mitochondrial number diminished, and cadmium in the renal cortex reached a saturation level. At this time interval, nearly 30% of cadmium in the whole cell fraction was found in the mitochondria. Cytochrome c oxidase (COX) activity in the proximal tubular epithelial cells decreased after 40-week exposure of cadmium. Oxidized phosphatidylcholine (oxPC) started to accumulate in the cytochrome c-positive mitochondria in some tubular epithelial cells after 80-week exposure. After 40 weeks, accumulation of the 4834-bp deletion in mitochondrial DNA was evident in both control and cadmium-treated groups. However, the amount of accumulated mitochondrial DNA deletion tended to increase after 40-week exposure, and was significantly greater after 80 weeks of exposure, compared to the control. Our results indicate that long-term cadmium exposure in rats accelerates accumulation of 4834-bp mitochondrial DNA deletions and impairment of mitochondrial function associated with accumulation of oxidized product.
Takaki
Aya
A
Department of Pathology, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonanku, 814-0180, Japan.
Jimi
Shiro
S
Segawa
Masaru
M
Hisano
Satoshi
S
Takebayashi
Shigeo
S
Iwasaki
Hiroshi
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000187:drug effects*; D000818:Animals; D002105:Cadmium Poisoning / Q000473:pathology*; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004272:DNA, Mitochondrial; D010713:Phosphatidylcholines; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV