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

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

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104 Scopus citations

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
DOIs
StatePublished - May 1994

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

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    Kribben, A., Wieder, E. D., 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. https://doi.org/10.1172/JCI117183