The Role of the Calcium-Dependent Enzymes Nitric Oxide Synthase and Calpain in Hypoxia-induced Proximal Tubule Injury
作者:
EdelsteinCharles L.,
YaqoobMohammad M.,
SchrierRobert W.,
期刊:
Renal Failure
(Taylor Available online 1996)
卷期:
Volume 18,
issue 3
页码: 501-511
ISSN:0886-022X
年代: 1996
DOI:10.3109/08860229609052821
出版商: Taylor&Francis
数据来源: Taylor
摘要:
A role of cytoplasmic free calcium [Ca2+]iin hypoxia-induced proximal tubule damage has been proposed. To further investigate the role of[Ca2+]iin mediating hypoxic proximal tubular injury, a video imaging technique has been developed in which [Ca2+]ican 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+]iwhich precedes evidence of membrane damage as assessed by PI staining. This rise in [Ca2+]iactivates 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+]iinitiating hypoxic injury by activating NOS and calpain.
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