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Titolo:
Significance and molecular targets of protein kinase A during cAMP-mediated protection of cold stored liver grafts
Autore:
Akbar, S; Minor, T;
Indirizzi:
Univ Bonn, Clin Surg, Div Surg Res, D-53127 Bonn, Germany Univ Bonn BonnGermany D-53127 Surg, Div Surg Res, D-53127 Bonn, Germany
Titolo Testata:
CELLULAR AND MOLECULAR LIFE SCIENCES
fascicolo: 11, volume: 58, anno: 2001,
pagine: 1708 - 1714
SICI:
1420-682X(200110)58:11<1708:SAMTOP>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
VENOUS OXYGEN PERSUFFLATION; NITRIC-OXIDE SYNTHASE; HEART-BEATING DONORS; PREDAMAGED LIVER; STELLATE CELLS; GASEOUS OXYGEN; PRESERVATION; APOPTOSIS; RAT; TRANSPLANTATION;
Keywords:
apoptosis; BAD; iNOS; ischemia; nitric oxide; stellate cell;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Minor, T Univ Bonn, Clin Surg, Div Surg Res, Siegmund Freud Str 25, D-53127 Bonn, Germany Univ Bonn Siegmund Freud Str 25 Bonn Germany D-53127 nn, Germany
Citazione:
S. Akbar e T. Minor, "Significance and molecular targets of protein kinase A during cAMP-mediated protection of cold stored liver grafts", CELL MOL L, 58(11), 2001, pp. 1708-1714

Abstract

The use of marginal donor livers is followed by a higher frequency of primary dys- or nonfunction after transplantation. The present study was designed to test the hypothesis that stimulation of the cAMP second-messenger signal pathway might protect the liver from ischemic injury, laying emphasis on the role of protein kinase A-mediated signal transduction. Rat livers were harvested after 45 min of cardiac arrest and preserved in HTK solution for 24 h. Hepatic integrity was assessed thereafter using a blood-free reperfusion model. Supplementation of the preservation solution with dibutyryl-cAMP (db-cAMP)promoted phosphorylation of BAD at Ser 112 and concomitantly mitigated mitochondrial release of cytochrome c into the cytosol. Apoptotic cell transformation was evident in reperfused livers by positive TUNEL-staining of sinusoidal lining cells and the detection of cleaved poly(ADP-ribose) polymerase (PAR-P) in tissue homogenates, by western analysis. Treatment with db-cAMP was effective in minimizing both TUNEL staining and PARP cleavage and significantly reduced postischemic enzyme leakage of alanine aminotransferase to one half, while hepatic bile production was enhanced by approximately 60% when compared to untreated livers. This functional improvement was accompanied by a net amelioration of portal vascular conductivity. Inhibition of A kinase-anchoring protein with HT31 completely reversed any of the observed effects obtained by db-cAMP. We conclude that enhancement of cellular cAMP signal maintains hepatic integrity during and after ischemic preservation which may be attributed to protein kinase A dependent phosphorylation of BAD in line with subsequent inhibition of mitochondria-initiated apoptosis of sinusoidal lining cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/02/20 alle ore 08:10:51