Involvement of p53-transactivated Puma in cisplatin-induced renal tubular cell death

Kazuhiko Tsuruya, Hideki Yotsueda, Hirofumi Ikeda, Masatomo Taniguchi, Kohsuke Masutani, Hideko Hayashida, Hideki Hirakata, Mitsuo Iida

研究成果: Contribution to journalArticle査読

28 被引用数 (Scopus)

抄録

Aims: The tumor suppressor protein p53 plays a critical role as a determinant of cell survival when cells are exposed to various toxic stresses, by preventing growth arrest, replication of damaged DNA, and apoptosis. A novel p53-dependent proapoptotic gene, Puma (p53 upregulated modulator of apoptosis) is thought to participate in this process. Recently, p53 was reported to play an essential role in cisplatin-induced renal tubular cell (RTC) death. The objective of the present study was to elucidate the roles of p53 and Puma in cisplatin-induced RTC death. Main methods: We examined the in vivo expression of p53 and Puma-α in the kidney and evaluated the modification of Puma-α expression and RTC death by in vitro treatment with pifithrin-α (PFT-α), a specific p53 inhibitor, or Puma-α-specific small interfering RNA (siRNA). Key findings: While no immunoreactivity for anti-p53- and anti-Puma-α antibody was detected in the control rat kidney, de novo expression of p53 and Puma-α was identified in the proximal tubular cells of the outer medulla at 6 h after cisplatin injection. Upregulation of these proteins preceded severe RTC injury. In vitro experiments revealed that PFT-α inhibited upregulation of Puma-α, and inhibition of Puma-α, either by PFT-α or by Puma-α-specific siRNA, decreased RTC death induced by 24-h cisplatin exposure. Significance: Our results indicated that p53 activation mediated cisplatin-induced RTC death through upregulation of Puma, and suggested that inhibition of p53 and Puma is beneficial for the prevention and treatment of cisplatin-induced acute renal failure.

本文言語英語
ページ(範囲)550-556
ページ数7
ジャーナルLife Sciences
83
15-16
DOI
出版ステータス出版済み - 10 10 2008

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)
  • 薬理学、毒性学および薬学(全般)

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