Downregulation of arginase II and renal apoptosis by inorganic mercury: overexpression of arginase II reduces its apoptosis.
Inorganic mercury is a toxic metal that accumulates in the proximal tubules of the kidney, causing apoptosis. Arginase II is known to inhibit apoptosis, but its role in the renal apoptosis caused by inorganic mercury is poorly understood. In the present study, we examined the involvement of arginase II in inorganic mercury-dependent apoptosis. A single exposure to mercuric chloride (HgCl(2), 1 mg/kg) in rats resulted in a dramatic time-dependent reduction in the activity of arginase II in the kidney; for example, the activity at 48 h after exposure was 31% of the control level. The decrease in arginase II activity was due to a decrease in the protein level, not to a reduction in gene expression or to direct inhibition of the activity itself. More interestingly, diminished arginase II activity was well correlated with the induction of apoptosis as evaluated by renal DNA fragmentation (r = 0.99). Overexpression of arginase II in LLC-PK(1) cells blocked cell death during exposure to inorganic mercury. These results suggest that inorganic mercury causes a reduction in protein levels of arginase II, and that impaired arginase II activity is, at least in part, associated with the apoptotic cell damage caused by this heavy metal.
Kanda
Hironori
H
University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.
Kikushima
Makoto
M
Homma-Takeda
Shino
S
Sumi
Daigo
D
Endo
Akiko
A
Toyama
Takashi
T
Miura
Nobuhiko
N
Naganuma
Akira
A
Kumagai
Yoshito
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001119:Arginase / Q000187:drug effects* / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018374:LLC-PK1 Cells; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D013997:Time Factors
D008627:Mercuric Chloride; C113162:Arg2 protein, rat; D001119:Arginase