Downregulation of arginase II and renal apoptosis by inorganic mercury: Overexpression of arginase II reduces its apoptosis

Hironori Kanda, Makoto Kikushima, Shino Homma-Takeda, Daigo Sumi, Akiko Endo, Takashi Toyama, Nobuhiko Miura, Akira Naganuma, Yoshito Kumagai

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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 (HgCl2, 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-PK1 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.

Original languageEnglish
Pages (from-to)67-73
Number of pages7
JournalArchives of Toxicology
Volume82
Issue number2
DOIs
Publication statusPublished - 2008 Feb 1

Keywords

  • Accumulation
  • Apoptosis
  • Arginase II
  • Inorganic mercury
  • Proximal tubule

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Downregulation of arginase II and renal apoptosis by inorganic mercury: Overexpression of arginase II reduces its apoptosis'. Together they form a unique fingerprint.

Cite this