A. Kribben et al., EVIDENCE FOR ROLE OF CYTOSOLIC-FREE CALCIUM IN HYPOXIA-INDUCED PROXIMAL TUBULE INJURY, The Journal of clinical investigation, 93(5), 1994, pp. 1922-1929
The role of cytosolic free Ca2+ ([Ca2+](i)) in hypoxic injury was inve
stigated 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) increa
sed from similar to 170 to similar to 390 nM during 5 min of hypoxia.
This increase preceded detectable cell injury as assessed by PI and wa
s reversible with reoxygenation. ,2-Bis(2-aminophenoxy)ethane-N,N,N',N
'-tetraacetic acid (BAPTA; 100 mu M) reduced [Ca2+](i) under basal con
ditions (similar to 80 nM) and during hypoxia (similar to 120 nM) and
significantly attenuated hypoxic injury. When [Ca2+](i) and hypoxic ce
ll injury were studied concurrently in the same individual tubules, th
e 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 in
dicate that in rat proximal tubules, hypoxia induces an increase of [C
a2+](i) which occurs before cell damage. The protective effect of BAPT
A supports a role for [Ca2+](i) in the initiation of hypoxic proximal
tubule injury. The glycine results, however, implicate calcium-indepen
dent mechanisms of injury and/or blockade of calcium-mediated processe
s of injury such as activation of phospholipases or proteases.