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Expression of the translational repressor NAT1 in experimental models of cardiac hypertrophy

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Abstract

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.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Queen's University, Kingston, ON, Canada, K7L 3N6

    S. Jeson Sangaralingham, Brian J. Pak, M. Yat Tse, Ekaterini Angelis & Stephen C. Pang

  2. Department of Pharmacology and Toxicology, Queen's University, Kingston, ON, Canada, K7L 3N6

    Michael A. Adams & C. Smallegange

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  1. S. Jeson Sangaralingham
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  2. Brian J. Pak
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  3. M. Yat Tse
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  4. Ekaterini Angelis
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  6. C. Smallegange
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  7. Stephen C. Pang
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Sangaralingham, S.J., Pak, B.J., Tse, M.Y. et al. Expression of the translational repressor NAT1 in experimental models of cardiac hypertrophy. Mol Cell Biochem 245, 183–190 (2003). https://doi.org/10.1023/A:1022884515544

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