Redistribution of cellular energy following renal ischemia

Autor: Karen M. Gaudio, Gunilla Thulin, Thomas Ardito, Michael Kashgarian, Norman J. Siegel
Rok vydání: 1991
Předmět:
Zdroj: Pediatric Nephrology. 5:591-596
ISSN: 1432-198X
0931-041X
DOI: 10.1007/bf00856647
Popis: In order to elucidate the pattern of redistribution of cellular energy and the restoration of basic cellular metabolism following an ischemic renal insult, suspensions enriched in proximal tubule segments were studied after 45 min of bilateral artery occlusion and 15 min and 2 h of reflow from rats given either normal saline (control), ATP-MgCl2 (which enhances postischemic recovery of ATP), or α, β-methyl adenosine diphosphate (AMPCP), which inhibits nucleotide degradation during ischemia. In non-ischemic control animals, approximately half of the energy is distributed to functional pump activity and half directed for non-transport purposes. When cellular ATP is reduced to 56% of control values, functional pump activity is significantly reduced to 61% of control, while energy delegated for non-transport purposes is decreased by a significantly smaller increment to only 78% of control at 15 min of reflow. In animals given ATP-MgCl2, the cellular and metabolic profile at 15 min of reflow was no different from ischemic control animals with cellular ATP levels similar at 58%. However, by 2 h, cellular ATP levels had increased significantly to 74%, and this was associated with a redistribution of cellular energy to functional pump activity (119% of control) with little change in non-transport function (76%). In animals treated with AMPCP, the cellular ATP levels were 74% of controls, similar to ATP-MgCl2-treated rats after 2 h of reflow. Despite the differences in reflow interval, the distribution of cellular energy was similar (functional pump activity 120% and non-transport activity 79%). By 2 h, cellular ATP was at 95% and both functional pump activity and non-transport activity were 100%. This early restoration of pump activity, followed by repletion of energy available for non-transport activity, is associated with minimal histological evidence of ischemic injury. These studies have shown: (1) a hierarchy of distribution of energy and maintenance of cellular metabolism; (2) there appears to exist a threshold requirement of ATP that is necessary to replete functional pump activity prior to redirecting energy for non-transport purposes; (3) energy redistribution following ischemia is not dependent upon time of reflow but upon replenishment of cellular energy; (4) repletion of transport and non-transport activities limits the degree of cellular damage.
Databáze: OpenAIRE
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