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Titolo:
Activation of the cAMP signaling pathway increases apoptosis in human beta-precursor cells and is associated with downregulation of Mcl-1 expression
Autore:
Myklebust, JH; Josefsen, D; Blomhoff, HK; Levy, FO; Naderi, S; Reed, LC; Smeland, EB;
Indirizzi:
Norwegian Radium Hosp, Dept Immunol, N-0310 Oslo, Norway Norwegian Radium Hosp Oslo Norway N-0310 pt Immunol, N-0310 Oslo, Norway Univ Oslo, Inst Basic Med Sci, Dept Biochem Med, Oslo, Norway Univ Oslo Oslo Norway nst Basic Med Sci, Dept Biochem Med, Oslo, Norway Univ Oslo, Natl Hosp, MSD Cardiovasc Res Ctr, Rikshosp, Oslo, Norway Univ Oslo Oslo Norway p, MSD Cardiovasc Res Ctr, Rikshosp, Oslo, Norway Univ Oslo, Natl Hosp, Inst Surg Res, Rikshosp, Oslo, Norway Univ Oslo Oslo Norway Natl Hosp, Inst Surg Res, Rikshosp, Oslo, Norway La Jolla Canc Res Fdn, Canc Res Ctr, Burnham Inst, La Jolla, CA 92037 USA La Jolla Canc Res Fdn La Jolla CA USA 92037 Inst, La Jolla, CA 92037 USA
Titolo Testata:
JOURNAL OF CELLULAR PHYSIOLOGY
fascicolo: 1, volume: 180, anno: 1999,
pagine: 71 - 80
SICI:
0021-9541(199907)180:1<71:AOTCSP>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT PROTEIN-KINASE; 3',5'-CYCLIC ADENOSINE-MONOPHOSPHATE; PROSTAGLANDIN E(2) RECEPTORS; HUMAN B-LYMPHOCYTES; MOUSE BONE-MARROW; CYCLIC-AMP; BCL-X; IMMUNOHISTOCHEMICAL ANALYSIS; TRANSGENIC MICE; FLOW-CYTOMETRY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Myklebust, JH Norwegian Radium Hosp, Dept Immunol, N-0310 Oslo, Norway Norwegian Radium Hosp Oslo Norway N-0310 0310 Oslo, Norway
Citazione:
J.H. Myklebust et al., "Activation of the cAMP signaling pathway increases apoptosis in human beta-precursor cells and is associated with downregulation of Mcl-1 expression", J CELL PHYS, 180(1), 1999, pp. 71-80

Abstract

During B- and T-cell ontogeny, extensive apoptosis occurs at distinct stages of development. Agents that increase intracellular levels of cAMP induceapoptosis in thymocytes and mature B cells, prompting us to investigate the role of cAMP signaling in human CD10(+) B-precursor cells. We show for the first time that forskolin (which increases intracellular levels of cAMP) increases apoptosis in the CD10+ cells in a dose-dependent manner (19%-94% with 0-1,000 mu M forskolin after 48 hours incubation, IC50 = 150 mu M). High levels of apoptosis were also obtained by exposing the cells to the cAMPanalogue 8-chlorophenylthio-cAMP (8-CPT-cAMP). Specific involvement of cAMP-dependent protein kinase (PKA) was demonstrated by the ability of a cAMP antagonist, Rp-isomer of 8-bromoadenosine- 3',. 5'-monophosphorothioate (Rp-8-Br-cAMPS), to reverse the apoptosis Increasing effect of the complementary cAMP agonist, Sp-8-Br-cAMPS. Furthermore, we investigated the expressionof Bcl-2 family proteins. We found that treatment of the cells with forskolin or 8-CPT-cAMP for 48 hours resulted in a fourfold decline in the expression of Mcl-1 (n = 6, P = 0.002) compared to control cells. The expression of Bcl-2, Bcl-x(L), or Bar was largely unaffected. Mature peripheral blood B cells showed a smaller increase in the percentage of apoptotic cells in response to 8-CPT-cAMP (1.3-fold, n = 6, P = 0.045) compared to B-precursor cells, and a smaller decrease in Mcl-1 levels (1.5-fold, n = 4, P = 0.014). Taken together, these findings show that cAMP is important in the regulation of apoptosis in B-progenitor and mature B cells and suggest that cAMP-increased apoptosis could be mediated, at least in part, by a decrease in Mcl-1 levels. (C) 1999 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 04:17:21