TY - JOUR
T1 - Expression of the translational repressor NAT1 in experimental models of cardiac hypertrophy
AU - Sangaralingham, S. Jeson
AU - Pak, Brian J.
AU - Tse, M. Yat
AU - Angelis, Ekaterini
AU - Adams, Michael A.
AU - Smallegange, C.
AU - Pang, Stephen C.
N1 - Funding Information:
The authors thank Dr. Thomas L. Innerarity of the Cardiovascular Research Institute and Department of Pathology, University of California, San Francisco, CA, USA for generously providing the polyclonal antibody against NAT1. Financial support for this research project was provided by the Heart and Stroke Foundation of Ontario, the Advisory Research Committee and the Garfield Kelly Cardiovascular Research and Development Fund, Queen’s University, Kingston, Ontario, Canada.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/3
Y1 - 2003/3
N2 - The development of hypertension-induced cardiac hypertrophy is a complex process involving a number of biochemical pathways. In particular, the translation initiation pathway has been postulated to play an important role in controlling cellular growth and proliferation in the cardiovascular system. Recently, a fundamental translational repressor, NAT1 (novel APOBEC target 1 ), has been identified. We have previously shown that NAT1 is developmentally-regulated in the heart of neonatal rats and its expression correlates with periods of rapid cardiac growth. The present investigation was designed to determine whether the expression of NAT1 is modified in the left ventricle of spontaneously hypertensive rats and 2-kidney-1-clip (2K1C) hypertensive rats. Northern blot analysis revealed an increase in NAT1 mRNA expression which correlates with the onset of cardiac hypertrophy. Unlike its pattern of mRNA expression, however, NAT1 protein level did not differ significantly from their respective controls throughout the time course. Interestingly, several protein species ranging in size from approximately 40-70 kDa were detected by Western blotting, in addition to the full length 97 kDa NAT1. Since the NAT1 transcript is a known substrate for the enzyme APOBEC-1 and possibly APOBEC-2, we speculate that these proteins may represent truncated fragments of NAT1 resulting from the formation of premature translation termination codons along the NAT1 transcript by APOBEC editing. Together, these results show that the ventricular expression of NAT1 is regulated at the transcriptional level during the early stages of genetic and 2K1C-induced hypertension and may be involved in the onset of left ventricular hypertrophy.
AB - The development of hypertension-induced cardiac hypertrophy is a complex process involving a number of biochemical pathways. In particular, the translation initiation pathway has been postulated to play an important role in controlling cellular growth and proliferation in the cardiovascular system. Recently, a fundamental translational repressor, NAT1 (novel APOBEC target 1 ), has been identified. We have previously shown that NAT1 is developmentally-regulated in the heart of neonatal rats and its expression correlates with periods of rapid cardiac growth. The present investigation was designed to determine whether the expression of NAT1 is modified in the left ventricle of spontaneously hypertensive rats and 2-kidney-1-clip (2K1C) hypertensive rats. Northern blot analysis revealed an increase in NAT1 mRNA expression which correlates with the onset of cardiac hypertrophy. Unlike its pattern of mRNA expression, however, NAT1 protein level did not differ significantly from their respective controls throughout the time course. Interestingly, several protein species ranging in size from approximately 40-70 kDa were detected by Western blotting, in addition to the full length 97 kDa NAT1. Since the NAT1 transcript is a known substrate for the enzyme APOBEC-1 and possibly APOBEC-2, we speculate that these proteins may represent truncated fragments of NAT1 resulting from the formation of premature translation termination codons along the NAT1 transcript by APOBEC editing. Together, these results show that the ventricular expression of NAT1 is regulated at the transcriptional level during the early stages of genetic and 2K1C-induced hypertension and may be involved in the onset of left ventricular hypertrophy.
KW - Cardiac hypertrophy
KW - Experimental hypertension
KW - Gene expression
KW - NAT1
KW - Translational repressor
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U2 - 10.1023/A:1022884515544
DO - 10.1023/A:1022884515544
M3 - Review article
C2 - 12708758
AN - SCOPUS:0037359233
SN - 0300-8177
VL - 245
SP - 183
EP - 190
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -