Abstract
Cyclic nucleotide-dependent vasorelaxation is associated with increases in the phosphorylation of a small heat shock-related protein, HSP20. We hypothesized that phosphorylation of HSP20 in vascular smooth muscles is associated with alterations in the macromolecular associations of HSP20. Treatment of bovine carotid artery smooth muscles with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, and the adenylate cyclase activator, forskolin, led to increases in the phosphorylation of HSP20 and dissociation of macromolecular aggregates of HSP20. However, 3-isobutyl-1-methylxanthine and forskolin treatment of a muscle that is uniquely refractory to cyclic nucleotide-dependent vasorelaxation, human umbilical artery smooth muscle, did not result in increases in the phosphorylation of HSP20 or to dissociation of macromolecular aggregates. HSP20 can be phosphorylated in vitro by the catalytic subunit of cAMP-dependent protein kinase (PKA) in both carotid and umbilical arteries and this phosphorylation of HSP20 is associated with dissociation of macromolecular aggregates of HSP20. Activation of cyclic nucleotide-dependent signaling pathways does not lead to changes in the macromolecular associations of another small heat shock protein, HSP27. Interestingly, the myosin light chains (MLC20) are in similar fractions as the HSP20, and phosphorylation of HSP20 is associated with changes in the macromolecular associations of MLC20. These data suggest that increases in the phosphorylation of HSP20 are associated with changes in the macromolecular associations of HSP20. HSP20 may regulate vasorelaxation through a direct interaction with specific contractile regulatory proteins.
Highlights
Cyclic nucleotide-dependent vasorelaxation is associated with increases in the phosphorylation of a small heat shock-related protein, HSP20
CAMP-dependent Phosphorylation—Treatment of strips of bovine carotid artery smooth muscle with the adenylyl cyclase activator, forskolin (10 M), and the phosphodiesterase inhibitor, IBMX (1 mM), for 10 min leads to increases in the phosphorylation of HSP20 (Fig. 1 and Table I)
In a muscle that is uniquely refractory to cyclic nucleotide-dependent relaxation, human umbilical smooth muscle (3), treatment with forskolin (10 M) and IBMX (1 mM) did not lead to significant increases in the phosphorylation of HSP20 (Fig. 1, Table I)
Summary
Vol 274, No 10, Issue of March 5, pp. 6324 –6329, 1999 Printed in U.S.A. Phosphorylation of the Small Heat Shock-related Protein, HSP20, in Vascular Smooth Muscles Is Associated with Changes in the Macromolecular Associations of HSP20*. Cyclic nucleotide-dependent vasorelaxation is associated with increases in the phosphorylation of a small heat shock-related protein, HSP20. 3-isobutyl-1-methylxanthine and forskolin treatment of a muscle that is uniquely refractory to cyclic nucleotide-dependent vasorelaxation, human umbilical artery smooth muscle, did not result in increases in the phosphorylation of HSP20 or to dissociation of macromolecular aggregates. Agonist pre-contracted bovine carotid artery smooth muscle relaxes with the addition of the guanylyl cyclase activator, sodium nitroprusside, or the adenylyl cyclase activator, forskolin This relaxation is associated with increases in the phosphorylation of the small heat shock-related protein, HSP201. HSP20 is not phosphorylated in a muscle that is uniquely refractory to cyclic nucleotide-dependent relaxation, human umbilical artery smooth muscle (3, 4) These data suggest that increases in the phosphorylation of HSP20 may mediate cellular signaling processes that lead to vasorelaxation. We postulated that HSP20 and/or HSP27 are cellular signaling molecules that regulate the state of contraction and relaxation of vascular smooth muscle
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