The role of the calcium-dependent enzymes nitric oxide synthase and calpain in hypoxia-induced proximal tubule injury.
A role of cytoplasmic free calcium [Ca2+]i in hypoxia-induced proximal tubule damage has been proposed. To further investigate the role of [Ca2+]i in mediating hypoxic proximal tubular injury, a video imaging technique has been developed in which [Ca2+]i can be measured simultaneously with propidium iodide (PI) staining of nuclei as an index of hypoxia-induced membrane damage. Hypoxia in rat proximal tubules is associated with a significant rise in [Ca2+]i which precedes evidence of membrane damage as assessed by PI staining. This rise in [Ca2+]i activates calpain, a Ca2+-dependent cysteine protease, and constitutive nitric oxide synthase (NOS), the Ca2+-dependent form of NOS. Inhibition of either calpain or nitric oxide synthase provides marked cytoprotection against hypoxic proximal tubular injury. These observations are consistent with the early rise in [Ca2+]i initiating hypoxic injury by activating NOS and calpain.
Edelstein
C L
CL
Department of Medicine, University of Colorado School of Medicine, Denver, 80262, USA.
Yaqoob
M M
MM
Schrier
R W
RW
D058186:Acute Kidney Injury / Q000209:etiology*; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000502:physiology*; D002154:Calpain / Q000502:physiology*; D015687:Cell Hypoxia; D003546:Cysteine Endopeptidases / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D007687:Kidney Tubules, Proximal; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000502:physiology*
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D002154:Calpain; D003546:Cysteine Endopeptidases; D002118:Calcium