ATP releases HSP-72 from protein aggregates after renal ischemia.
The pattern of 72-kDa heat-shock protein (HSP-72) induction after renal ischemia suggests a role in restoring cell structure. HSP-72 activity in the repair and release from denatured and aggregated proteins requires ATP. Protein aggregates were purified from normal and ischemic rat renal cortex. The addition of ATP to cortical homogenates reduced HSP-72, Na(+)-K(+)-ATPase, and actin in aggregates subsequently isolated, suggesting that their interaction is ATP dependent. Altering ATP hydrolysis in the purified aggregates, however, had different effects. ATP released HSP-72 during reflow and preserved Na(+)-K(+)-ATPase association with aggregates at 2 h but had no effect in controls or at 6 h reflow and caused no change in actin. These results indicate that HSP-72 complexes with aggregated cellular proteins in an ATP-dependent manner and suggests that enhancing HSP-72 function after ischemic renal injury assists refolding and stabilization of Na(+)-K(+)-ATPase or aggregated elements of the cytoskeleton, allowing reassembly into a more organized state.
Aufricht
C
C
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA.
Lu
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E
Thulin
G
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Kashgarian
M
M
Siegel
N J
NJ
Van Why
S K
SK
D000199:Actins / Q000032:analysis; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D003599:Cytoskeleton / Q000201:enzymology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D006868:Hydrolysis; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis / Q000378:metabolism*
D000199:Actins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011506:Proteins; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase