A major interest of our laboratory is the mechanism by which the cardiovascular system adapts to physiological and pathological stress. Part of this response to stress involves the expression of different isoforms of the contractile and regulatory proteins. Our focus is on the relation between structural features, specific to isoforms of the regulatory and contractile proteins, to the functional properties of the muscle cell. Currently we are investigating the regulation of the expression of alternately spliced isoforms of smooth muscle myosin heavy chain and their functional significance. We are able to detect four different isoforms of myosin, two differ at the C-terminus and we have developed antibodies that are specific for these two isoforms. There is also a splice site at the N-terminus near the ATPase site and these isoforms can be detected at the mRNA level by the polymerase chain reaction. The isoforms are differentially distributed in different smooth muscle tissues and the N-terminal isoforms differ in ATPase activity. In particular we are studying the effect of estrogen deprivation and replacement on myosin isoform expression and associated changes in contractile function in vascular tissue. Our hypothesis is that the effect of estrogen on the functional properties of vascular smooth muscle contributes to the protective effect of estrogen on the heart.
Publications:
1. Martin, A.F., Bhatti, S. and Paul, R.J. C-terminal isoforms of the myosin heavy chain and smooth muscle function. Comparative Biochem. Physiol., 117B:3-11, 1997.
2. Rarick, H.M., Tu, X-H., Solaro, R.J. and Martin, A.F. The C-terminus of cardiac troponin I is essential for full inhibitory activity and Ca-sensitivity of rat myofibrils. J. Biol. Chem., 272:26887-26892, 1997.
3. Rarick, H.M., Tang, H-P., Guo, X-D., Martin, A.F. and Solaro, R.J. Interactions at the NH2-terminal interface of cardiac troponin I modulate myofilament activation. J. Mol. Cell. Cardiol., 31:363-375, 1999.
4. Fentzke, R.C., Buck, S.H., Patel, J.R., Lin, H., Wolska, B.M., Stojanovic, M.O., Martin, A.F., Solaro, R.J., Moss, R.L. and Leiden, J.M. Impaired cardiomyocyte relaxation and diastolic function in transgenic mice expressing slow skeletal troponin I in the heart. J. Physiol. (London), 517:143-157, 1998.
5. Bhatti, S., Manaves, V. and Martin, A.F. Effect of 17b-estradiol on the expression of mRNA for the N-terminal myosin isoforms in rat vascular smooth muscle. Submitted 1999.