Endoplasmic reticulum Ca2+ signaling and calpains mediate renal cell death

J. F. Harriman, X. L. Liu, M. D. Aleo, Khaled Machaca, R. G. Schnellmann

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The goal of the current study was to determine the roles of ATP content, endoplasmic reticulum (ER) Ca2+ stores, cytosolic free Ca2+ (Ca2+ f) and calpain activity in the signaling of rabbit renal proximal tubular (RPT) cell death (oncosis). Increasing concentrations (0.3-10 μM) of the mitochondrial inhibitor antimycin A produced rapid ATP depletion that correlated to a rapid and sustained increase in Ca2+ f, but not phospholipase C activation. The ER Ca2+-ATPase inhibitors thapsigargin (5 μM) or cyclopiazonic acid (100 μM) alone produced similar but transient increases in Ca2+ f. Pretreatment with thapsigargin prevented antimycin A-induced increases in Ca2+ f and antimycin A pretreatment prevented thapsigargin-induced increases in Ca2+ f. Calpain activity increased in conjunction with ER Ca2+ release. Pretreatment, but not post-treatment, with thapsigargin or cyclopiazonic acid prevented antimycin A-induced cell death. These data demonstrate that extensive ATP depletion signals oncosis through ER Ca2+ release, a sustained increase in Ca2+ f and calpain activation. Depletion of ER Ca2+ stores prior to toxicant exposure prevents increases in Ca2+ f and oncosis.

Original languageEnglish
Pages (from-to)734-741
Number of pages8
JournalCell Death and Differentiation
Volume9
Issue number7
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Calpain
Antimycin A
Thapsigargin
Endoplasmic Reticulum
Cell Death
Kidney
Adenosine Triphosphate
Calcium-Transporting ATPases
Type C Phospholipases
Rabbits

Keywords

  • Calcium
  • Calpain
  • Cell death
  • Endoplasmic reticulum
  • Oncosis
  • Renal proximal tubule

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Endoplasmic reticulum Ca2+ signaling and calpains mediate renal cell death. / Harriman, J. F.; Liu, X. L.; Aleo, M. D.; Machaca, Khaled; Schnellmann, R. G.

In: Cell Death and Differentiation, Vol. 9, No. 7, 2002, p. 734-741.

Research output: Contribution to journalArticle

Harriman, J. F. ; Liu, X. L. ; Aleo, M. D. ; Machaca, Khaled ; Schnellmann, R. G. / Endoplasmic reticulum Ca2+ signaling and calpains mediate renal cell death. In: Cell Death and Differentiation. 2002 ; Vol. 9, No. 7. pp. 734-741.
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