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R. W. Wiseman, Department of Radiology, University of Washington School of Medicine, Seattle, WA 98195,
Departments of Radiology and Physiology and Biophysics and Center for Bioengineering, University of Washington School of Medicine, Seattle, WA 98195,
Department of Microbial Physiology, Faculty of Biology, Free University, 1081 HV Amsterdam; and, E. C. Slater Institute, Biocenter, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands,
The following is the abstract of the article discussed in the subsequent letter:
Portman, Michael A., Yun Xiao, Ying Song,
and Xue-Han Ning. Expression of adenine nucleotide translocator
parallels maturation of respiratory control in heart in vivo.
Am. J. Physiol. 273 (Heart Circ. Physiol. 42):
H1977-H1983, 1997.
Changes in the relationship between myocardial
high-energy phosphates and oxygen consumption in vivo occur during
development, implying that the mode of respiratory control undergoes
maturation. We hypothesized that these maturational changes in sheep
heart are paralleled by alterations in the adenine nucleotide
translocator (ANT), which are in turn related to changes in the
expression of this gene. Increases in myocardial oxygen consumption
(M
O2) were induced by
epinephrine infusion in newborn (0-32 h,
n = 6) and mature sheep (30-32
days, n = 6), and high-energy
phosphates were monitored with 31P
nuclear magnetic resonance. Western blot analyses for the
ANT1 and the
-subunit of
F1-adenosinetriphosphatase
(ATPase) were performed in these hearts and additional
(n = 9 total per group) as well as in
fetal hearts (130-132 days of gestation,
n = 5). Northern blot analyses were
performed to assess for changes in steady-state RNA transcripts for
these two genes. Kinetic analyses for the
31P spectra data revealed that the
ADP-M
O2 relationship for
the newborns conformed to a Michaelis-Menten model but that the mature data did not conform to first- or second-order kinetic control of
respiration through ANT. Maturation from fetal to mature was accompanied by a 2.5-fold increase in ANT protein (by Western blot),
with no detectable change in
-F1-ATPase. Northern blot data
show that steady-state mRNA levels for ANT and
-F1-ATPase increased
~2.5-fold from fetal to mature. These data indicate that
1) respiratory control pattern in
the newborn is consistent with a kinetic type regulation through ANT,
2) maturational decreases in control
through ANT are paralleled by specific increases in ANT content, and
3) regulation of these changes in
ANT may be related to increases in steady-state transcript levels for
its gene.
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