Postischemic thyroxin stimulates renal mitochondrial adenine nucleotide translocator activity.
Postischemic thyroxin (T4) enhances restitution of cellular ATP and accelerates recovery of renal function. This effect is not related to global improvement in cell integrity. To determine the mechanism by which recovery of cellular ATP is enhanced, the effect of T4 on mitochondrial ATP production was evaluated using specific inhibitor stop assays for mitochondrial phosphate transport and ADP translocator activity. Rats were subjected to 45-min renal ischemia and given normal saline (NS, 0.5 ml) or T4 (20 micrograms/kg) during the reflow period. By 30-min reflow; the values for apparent endpoint of phosphate transport (PiTm, nmol Pi/mg mitochondrial protein) had recovered to rates seen in nonischemic animals (10.3 +/- 0.9) and remained stable at 120 min. T4 treatment did not affect PiTm. In contrast, the apparent endpoint of ADP transport (ADPTm, nmol ADP/mg mitochondrial protein) was dramatically decreased in NS rats at 30-min (6.7 +/- 0.5) and 120-min (13.7 +/- 1.0) reflow compared with nonischemic control rats (24.7 +/- 2.4). T4 significantly improved ADPTm by 30 min (10.1 +/- 0.6, P < 0.05). By 120 min T4 stimulated ADPTm (37.7 +/- 5.2, P < 0.05) to exceed nonischemic control values. These data suggest the following: 1) postischemic mitochondrial PiTm recovers to control values by 30 min of reflow; 2) T4 does not augment PiTm; 3) renal ischemia causes a dramatic decrease in mitochondrial ADPTm; 4) postischemic T4 significantly enhances mitochondrial nucleotide transport at 30-min reflow; 5) by 120-min reflow, T4 rats have ADPTm which exceeds control values.(ABSTRACT TRUNCATED AT 250 WORDS)
Boydstun
I
I
Department of Pediatrics and Pathology, Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA.
Najjar
S
S
Kashgarian
M
M
Carpenter
T
T
Siegel
N
N
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D015424:Reperfusion; D013974:Thyroxine / Q000494:pharmacology*
D010710:Phosphates; D000244:Adenosine Diphosphate; D013974:Thyroxine