Browse > Article

Transgelin is Required for Agonist-induced $Ca^{2+}$-Sensitization in Vascular Contractility: Evidence from an Antisense Approach  

Je, Hyun-Gon (Department of pediatrics, CHA Gangnam Medical Center, CHA University)
Je, Hyun-Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
Publication Information
YAKHAK HOEJI / v.53, no.3, 2009 , pp. 156-160 More about this Journal
Abstract
The present study was undertaken to determine whether transgelin participates in the regulation of vascular smooth muscle contraction and, if so, to investigate the mechanism. By PCR homology cloning, the cDNA sequence of ferret transgelin was determined and phosphorothioate antisense and random oligonucleotides were synthesized and introduced into strips of ferret aorta by a chemical loading procedure. Treatment of ferret aorta with transgelin antisense oligonucleotides resulted in a significant decrease in protein levels of transgelin to sham- or random sequence-loaded muscles, but no change in the protein levels of actin. Contraction in response to a phorbol ester was significantly decreased in antisense-treated muscles compared to sham- or random sequence-loaded controls. Neither basal intrinsic tone nor the contraction in response to phenylephrine was significantly affected by the antisense treatment. The data indicate that transgelin plays a significant role in the regulation of contraction and suggest that in a tonically active smooth muscle transgelin may function as a signalling protein to facilitate PKC or ERK-dependent signalling rather than thick filament regulation including $Ca^{2+}$ or calmodulin dependent regulation of myosin light chain kinase.
Keywords
phenylephrine; phorbol ester; PKC; vasoconstriction; vasorelaxation;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Lees-Miller, J. P., Heeley, D. H. and Smillie, L. B. : An abundant and novel protein of 22 kDa (SM22) is widely distributed in smooth muscles. Purification form bovine aorta. Biochem. J. 244, 705 (1987)   DOI
2 Shanahan, C. M., Weissberg, P. L. and Metcalfe, J. C. : Isolation of gebe markers of differentiated and proliferating vascular smooth muscle cells. Circ. Res. 73, 193 (1993)   DOI   PUBMED   ScienceOn
3 Bregant, E., Renzone, G., Lonigro, R., Passon, N., Di Loreto, C., Pandolfi, M., Scaloni, A., Tell, G. and Damante, G. : Downregulation of SM22/transgelin gene expression during H9c2 cells differentiation. Moll. Cell. Biochem. 2009 Feb 18. [Epub ahead of print]
4 Somlyo, A. P. and Somlyo, A. V. : From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta. Physiol. Scand. 164, 437 (1998)   DOI   ScienceOn
5 Sakurada, S., Takuwa, N., Sugimoto, N., Wang, Y., Seto, M., Sasaki, Y. and Takuwa, Y. : Ca2+-dependent activation of Rho and Rho-kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circ. Res. 93, 548 (2003)   DOI   ScienceOn
6 Samaha, F. F., Ip, H. S., Morrisey, E. E., Seltzer, J., Tang, Z., Solway, J. and Parmacek, M. S. : Developmental pattern of expression and genomic organization of the calponin-h1 gene; a contractile smooth muscle cell marker. J. Biol. Chem. 271,395 (1996)   DOI
7 Thweatt, R., Lumpkin, C. K. and Goldstein, S. : A novel gene encoding a smooth muscle protein is overexpressed in senescent human fibroblasts. Biochem. Biophys. Res. Commun.187, 1 (1992)   DOI   ScienceOn
8 Ayme-Southgate, A., Lasko, P., French, C. and Pardue, M. L. : Characterization of the gene for mp20: a Drosophila muscle protein that is not found in asynchronous oscillatory flight muscle. J. Cell Biol. 108, 521 (1989)
9 Lawson, D., Harrison, M. and Shapland, C. : Fibroblast transgelin and smooth muscle SM22alpha are the same protein, the expression of which is down-regulated in many cell lines. Cell Motil. Cytoskel. 38, 250 (1997)   DOI   ScienceOn
10 Leung, T., Manser, E., Tan, L. and Lim, L. : A novel serine/ threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes. J. Biol. Chem. 270, 29051 (1995)   DOI
11 Kim, I., Je H. D., Gallant, C., Zhan, Q., Riper, D. V., Badwey, J. A., Singer, H. A. and Morgan, K. G. : $Ca^{2+}$-calmodulindependent protein kinase II-dependent activation of contractility in ferret aorta. J. Physiol. 526, 367 (2000)   DOI   ScienceOn
12 Somlyo, A. P. and Somlyo, A. V. : Signal transduction and regulation in smooth muscle. Nature 372, 231 (1994)   DOI   ScienceOn
13 Kitazawa, T., Masuo, M. and Somlyo, A. P. : Protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. Proc. Natl. Acad. Sci. USA 88, 9307 (1991)   DOI   ScienceOn
14 Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M. and Narumiya, S. : Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389, 990-994 (1997)   DOI   ScienceOn
15 Matsui, T., Amano, M., Yamamoto, T., Chihara, K., Nakafuku, M., Ito, M., Nakano, T., Okawa, K., Iwamatsu, A. and Kaibuchi, K. : Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO. J. 15, 2208 (1996)
16 Wier, W. G. and Morgan, K. G. : 1-Adrenergic signaling mechanisms in contraction of resistance arteries. Rev. Physiol. Biochem. Pharmacol. 150, 91 (2003)
17 Goetinck, S. and Waterston, R. H. : The Caenorhabditis elegans muscle-affecting gene unc-87 encodes a novel thin filament associated protein. J. Cell Biol. 127, 79 (1994)   DOI   ScienceOn
18 Somlyo, A. P. and Somlyo, A. V. : Signal transduction and regulation in smooth muscle. Nature 372, 231 (1994)   DOI   ScienceOn
19 Ren, W., Ng, G. Y. K., Wang, R.-X., Wu, P. H., O'Dowd, B. F., George, S., Osmond, D. H. and Liew, C. : The identification of NP25: a novel protein that is differentially expressed by neuronal subpopulations. Mol. Brain Res. 22, 173 (1994)   DOI   ScienceOn
20 Takahashi, K. and Nadal-Ginard, B. : Molecular cloning and sequence analysis of smooth muscle calponin. J. Biol. Chem. 266, 13284 (1991)
21 Gohla, A., Schultz, G. and Offermanns, S. : Roles for G(12)/ G(13) in agonist-induced vascular smooth muscle cell contraction. Circ. Res. 87, 221 (2000)   DOI   PUBMED   ScienceOn
22 Almendral, J. M., Santaren, J. F., Perera, J., Zerial, M. and Bravo, R. : Expression, cloning and cDNA sequence of a fibroblast serum-regulated gene encoding a putative actinassociated protein (p27). Exp. Cell. Res. 181, 518 (1989)   DOI   ScienceOn