Evidence for role of cytosolic free calcium in hypoxia-induced proximal tubule injury

Andreas Kribben, Eric Wieder, Jack F M Wetzels, Luis Yu, Patricia E. Gengaro, Thomas J. Burke, Robert W. Schrier

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

The role of cytosolic free Ca2+ ([Ca2+](i)) in hypoxic injury was investigated in rat proximal tubules. [Ca2+](i) was measured using fura-2 and cell injury was estimated with propidium iodide (PI) in individual tubules using video imaging fluorescence microscopy. [Ca2+](i) increased from ~ 170 to ~ 390 nM during 5 min of hypoxia. This increase preceded detectable cell injury as assessed by PI and was reversible with reoxygenation. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA; 100 μM) reduced [Ca2+](i) under basal conditions (~ 80 nM) and during hypoxia (~ 120 nM) and significantly attenuated hypoxic injury. When [Ca2+](i) and hypoxic cell injury were studied concurrently in the same individual tubules, the 10 min [Ca2+](i) rise correlated significantly with subsequent cell damage observed at 20 min. 2 mM glycine did not block the rise in [Ca2+](i), yet protected the tubules from hypoxic injury. These results indicate that in rat proximal tubules, hypoxia induces an increase of [Ca2+](i) which occurs before cell damage. The protective effect of BAPTA supports a role for [Ca2+](i) in the initiation of hypoxic proximal tubule injury. The glycine results, however, implicate calcium-independent mechanisms of injury and/or blockade of calcium-mediated processes of injury such as activation of phospholipases or proteases.

Original languageEnglish (US)
Pages (from-to)1922-1929
Number of pages8
JournalJournal of Clinical Investigation
Volume93
Issue number5
StatePublished - May 1994
Externally publishedYes

Fingerprint

Calcium
Wounds and Injuries
Propidium
Glycine
Hypoxia
Phospholipases
Fura-2
Fluorescence Microscopy
Peptide Hydrolases
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid

Keywords

  • adenosine triphosphate
  • BAPTA
  • computer-assisted image processing
  • fura-2
  • propidium iodide

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kribben, A., Wieder, E., Wetzels, J. F. M., Yu, L., Gengaro, P. E., Burke, T. J., & Schrier, R. W. (1994). Evidence for role of cytosolic free calcium in hypoxia-induced proximal tubule injury. Journal of Clinical Investigation, 93(5), 1922-1929.

Evidence for role of cytosolic free calcium in hypoxia-induced proximal tubule injury. / Kribben, Andreas; Wieder, Eric; Wetzels, Jack F M; Yu, Luis; Gengaro, Patricia E.; Burke, Thomas J.; Schrier, Robert W.

In: Journal of Clinical Investigation, Vol. 93, No. 5, 05.1994, p. 1922-1929.

Research output: Contribution to journalArticle

Kribben, A, Wieder, E, Wetzels, JFM, Yu, L, Gengaro, PE, Burke, TJ & Schrier, RW 1994, 'Evidence for role of cytosolic free calcium in hypoxia-induced proximal tubule injury', Journal of Clinical Investigation, vol. 93, no. 5, pp. 1922-1929.
Kribben A, Wieder E, Wetzels JFM, Yu L, Gengaro PE, Burke TJ et al. Evidence for role of cytosolic free calcium in hypoxia-induced proximal tubule injury. Journal of Clinical Investigation. 1994 May;93(5):1922-1929.
Kribben, Andreas ; Wieder, Eric ; Wetzels, Jack F M ; Yu, Luis ; Gengaro, Patricia E. ; Burke, Thomas J. ; Schrier, Robert W. / Evidence for role of cytosolic free calcium in hypoxia-induced proximal tubule injury. In: Journal of Clinical Investigation. 1994 ; Vol. 93, No. 5. pp. 1922-1929.
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