AJP - Endocrinology and Metabolism, Vol 268, Issue 4 E651-E656, Copyright © 1995 by American Physiological Society
Postischemic thyroxin stimulates renal mitochondrial adenine nucleotide translocator activity
I. Boydstun, S. Najjar, M. Kashgarian, T. Carpenter and N. Siegel
Department of Pediatrics and Pathology, Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA.
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)
