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Titolo:
Smad7 is induced by norepinephrine and protects rat hepatocytes from activin A-induced growth inhibition
Autore:
Kanamaru, C; Yasuda, H; Takeda, M; Ueda, N; Suzuki, J; Tsuchida, T; Mashima, H; Ohnishi, H; Fujita, T;
Indirizzi:
Univ Tokyo, Sch Med, Dept Med, Tokyo 1138655, Japan Univ Tokyo Tokyo Japan 1138655 , Sch Med, Dept Med, Tokyo 1138655, Japan
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 49, volume: 276, anno: 2001,
pagine: 45636 - 45641
SICI:
0021-9258(200112)276:49<45636:SIIBNA>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; TGF-BETA RECEPTOR; LIVER-REGENERATION; DNA-SYNTHESIS; AUTOCRINE INHIBITOR; PARTIAL-HEPATECTOMY; GENE-EXPRESSION; ACTIVATION; CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Yasuda, H Univ Tokyo, Sch Med, Dept Med, 7-3-1 Hongo, Tokyo 1138655, JapanUniv Tokyo 7-3-1 Hongo Tokyo Japan 1138655 Tokyo 1138655, Japan
Citazione:
C. Kanamaru et al., "Smad7 is induced by norepinephrine and protects rat hepatocytes from activin A-induced growth inhibition", J BIOL CHEM, 276(49), 2001, pp. 45636-45641

Abstract

Activin A induces growth arrest of rat hepatocytes in vitro and in vivo. The alpha (1)-adrenergic agonist, norepinephrine (NE), enhances epidermal growth factor-stimulated DNA synthesis and inhibits activin A-induced growth inhibition, but the mechanisms of these actions are unclear. Smad proteins have recently been identified as intracellular signaling mediators of transforming growth factor-beta family members. In the present study, we explored how NE modulates the Smad signaling pathway in rat cultured hepatocytes. We demonstrate that NE inhibits activin A-induced nuclear accumulation of Smad2/3 and that NE rapidly induces inhibitory Smad7 mRNA expression. Infection of Smad7 adenovirus into rat hepatocytes inhibited activin A-induced nuclear accumulation of Smad2/3, enhanced epidermal growth factor-stimulated DNA synthesis, and abolished the growth inhibitory effect of activin A. We also demonstrated that the induction of Smad7 by NE is dependent on nuclearfactor-kappaB (NF-kappaB). The amount of active NF-kappaB complex rapidly increased after NE treatment. Preincubation of the cells with an NF-kappaB pathway inhibitor N-tosyl-L-phenylalanine chloromethyl ketone or infection of the cells with an adenovirus expressing an I kappaB super-repressor (Ad5I kappaB) abolished the NE-induced Smad7 expression. These results indicatea mechanism of transmodulation between the Smad and trimeric G protein signaling pathways in rat hepatocytes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/20 alle ore 20:54:48