Year: 1994
Type: article
Abstract: The role of cytosolic free Ca2" (ICa2"j,) in hypoxic injury was investigated in rat proximal tubules.[Ca21]i was measured using fura-2 and cell injury was estimated with propidium iodide (PI) in individual tubules using video imaging fluorescence micros- copy.[Ca2"j, 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 ,M) reduced [Ca2+ji under basal conditions (-80 nM) and during hypoxia (-120 nM) and significantly attenuated hypoxic injury.When ICa2"Ji 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 ICa2+I,, yet protected the tubules from hypoxic injury.These results indicate that in rat proximal tubules, hypoxia induces an increase of [Ca2+1i which occurs before cell damage.The protec- tive effect of BAPTA supports a role for [Ca2+1i in the initiation of hypoxic proximal tubule injury.The glycine results, how- ever, implicate calcium-independent mechanisms of injury and/ or blockade of calcium-mediated processes of injury such as activation of phospholipases or proteases.(J.Clin.Invest.1994.93:1922-1929.) Key words: propidium iodide * fura-2 computer-assisted image processing * BAPTA * adenosine triphosphate Ca2+, as assessed by atomic absorption, occurs in tubules during hypoxia (4, 5), whether this cellular Ca2+ overload is partly retained in the cytosol or completely accumulated by mito- Parts of this work were presented at the 25th Meeting of the American
DOI: 10.1172/jci117183
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2114799546