| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 29, 22213-22219, July 21, 2000
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the The mechanisms by which ethanol inhibits
hepatocyte proliferation have been a source of some considerable
investigation. Our studies have suggested a possible role for tissue
transglutaminase (tTG) in this process. Others have shown that tTG has
two distinctly different functions: it catalyzes protein cross-linking,
which can lead to apoptosis and enhancement of extracellular matrix stability, and it can function as a G protein
(G
Roles of Tissue Transglutaminase in Ethanol-induced Inhibition of
Hepatocyte Proliferation and
1-Adrenergic Signal Transduction*
§,
Department of Internal Medicine and
Transplant Research Program, University of California Davis Medical
Center, Sacramento, California 95817 and the Departments of
§ Medicine and ¶ Pathology, Anatomy, and Cell Biology,
Jefferson Medical College, Thomas Jefferson University,
Philadelphia, Pennsylvania 19107
h). Under that circumstance, we speculated that
the cross-linking activity would be decreased and that it would
function to enhance hepatocyte proliferation in response to adrenergic
stimulation. Ethanol treatment inhibited hepatocyte proliferation and
led to enhanced tTG cross-linking activity, whereas treatment of
hepatocytes with an 1 adrenergic agonist, phenylephrine, enhanced
hepatocyte proliferation while decreasing tTG cross-linking. However,
phenylephrine treatment of several hepatoma cell lines had no effect on
cellular proliferation or tTG cross-linking activity, and of note,
Northern blot analysis demonstrated that whereas primary hepatocytes
had high levels of the 1
adrenergic receptor (1BAR) mRNA,
the hepatoma cell lines did not have this mRNA. When the Hep
G2 cell line was stably transduced with an expression
vector containing the 1BR cDNA, the cell line responded to
phenylephrine treatment with enhanced proliferation and with decreased
tTG cross-linking activity. Ethanol treatment of the
1BAR-transfected cells suppressed the phospholipase C-mediated
signaling pathways, as detected in the phenylephrine-induced Ca2+ response. These results suggest that phenylephrine
stimulation of hepatocyte proliferation appears to be occurring through
the 1BAR, which is known to be coupled with the tTG G protein
moiety, Gh, and that tTG appears to play a significant
role in either enhancing or inhibiting hepatocyte proliferation,
depending on its cellular location and on whether it functions as a
cross-linking enzyme or a G protein.
*
This work was supported in part by National Institutes of
Health Grants DK-41875 and AA-06386 (to M. A. Z.) and DK09762 (to J. W.). Presented at the 50th annual meeting of American Association for the Study of Liver Disease, November 5-9, 1999 (Dallas, TX) and
published in an abstract form in (1999) Hepatology
30: 337A.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: University of
California Davis Medical Center, Transplant Research Program, 4635 2nd
Ave., Suite 1001, Sacramento, CA 95817. Tel.: 916-734-8063; Fax:
916-734-8097; E-mail: mazern@ucdavis.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M Dupuis, E Houdeau, and S Mhaouty-Kodja Increased potency of {alpha}1-adrenergic receptors to induce inositol phosphates production correlates with the up-regulation of {alpha}1d/Gh{alpha}/phospholipase C{delta}1 signaling pathway in term rat myometrium Reproduction, January 1, 2008; 135(1): 55 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Kang, K. S. Yi, N. S. Kwon, K.-H. Park, U.-H. Kim, K. J. Baek, and M.-J. Im {alpha}1B-Adrenoceptor Signaling and Cell Motility: GTPase FUNCTION OF Gh/TRANSGLUTAMINASE 2 INHIBITS CELL MIGRATION THROUGH INTERACTION WITH CYTOPLASMIC TAIL OF INTEGRIN {alpha} SUBUNITS J. Biol. Chem., August 27, 2004; 279(35): 36593 - 36600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dupuis, A. Levy, and S. Mhaouty-Kodja Functional Coupling of Rat Myometrial {alpha}1-Adrenergic Receptors to Gh{alpha}/Tissue Transglutaminase 2 during Pregnancy J. Biol. Chem., April 30, 2004; 279(18): 19257 - 19263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Zhang, R. Vezza, T. Plappert, P. McNamara, J. A. Lawson, S. Austin, D. Pratico, M. S.-J. Sutton, and G. A. FitzGerald COX-2-Dependent Cardiac Failure in Gh/tTG Transgenic Mice Circ. Res., May 30, 2003; 92(10): 1153 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Lu, A. Strohecker, and J.-h. Ou Post-translational Modification of the Hepatitis C Virus Core Protein by Tissue Transglutaminase J. Biol. Chem., December 14, 2001; 276(51): 47993 - 47999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Baek, S. K. Kang, D. S. Damron, and M.-J. Im Phospholipase Cdelta 1 Is a Guanine Nucleotide Exchanging Factor for Transglutaminase II (Galpha h) and Promotes alpha 1B-Adrenoreceptor-mediated GTP Binding and Intracellular Calcium Release J. Biol. Chem., February 16, 2001; 276(8): 5591 - 5597. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
