Actin cytoskeleton derangement induces apoptosis in renal ischemia/reperfusion.
This study evaluated whether cytoskeletal alterations during the ischemic conditions associated with kidney preservation could determine apoptosis. Cytoskeletal alterations are among the main effects of ischemia and may induce apoptosis. Rat kidneys were preserved in University of Wisconsin (UW) solution for 24 h. Some groups of animals underwent 45 min of warm ischemia (WI) to evaluate its effect on both the actin cytoskeleton and apoptosis (assessed by caspase-3 activity and TUNEL staining). Swinholide A (SwinA) and Latrunculin B (LB), two actin cytoskeleton-targeted agents, were administered to assess the effect of direct actin disruption on apoptosis. Jasplakinolide (JP), a compound that stabilizes actin filaments, was administered to evaluate the effect of actin stabilization. Apoptosis was evaluated at 3 h of ex vivo reperfusion using the isolated perfused rat kidney (IPK) model.


RESULTS
Apoptosis increased during reperfusion with WI or administration of actin disruptor agents. Administration of stabilizing agents reversed apoptosis in kidneys that had previously undergone WI or had received an actin disruptor agent.


CONCLUSIONS
The disruption of the actin cytoskeleton during ischemic conditions associated with kidney preservation induces apoptosis upon reperfusion through caspase-3 activation.
Genescà
M
M
Department of Experimental Pathology, IIBB-CSIC, IDIBAPS, Barcelona, Spain.
Sola
A
A
Hotter
G
G
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure*; D000818:Animals; D017209:Apoptosis; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D007668:Kidney / Q000098:blood supply* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology*; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D019086:Bridged Bicyclo Compounds, Heterocyclic; D008387:Marine Toxins; D013844:Thiazoles; D053778:Thiazolidines; C086235:swinholide A; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C037068:latrunculin B