Phosphatidylethanol mimics ethanol modulation of p42/44 mitogen-activated protein kinase signalling in hepatocytes

被引：13

作者：

Aroor, AR ^{[1
]}

Custer, GW ^{[1
]}

Weng, YI ^{[1
]}

Lee, YJ ^{[1
]}

Shukla, SD ^{[1
]}

机构：

[1] Univ Missouri, Sch Med, Dept Pharmacol, Columbia, MO 65212 USA

来源：

ALCOHOL AND ALCOHOLISM | 2002年 / 37卷 / 06期

关键词：

D O I：

10.1093/alcalc/37.6.534

中图分类号：

R194 [卫生标准、卫生检查、医药管理];

学科分类号：

摘要：

Aims: Although long-term exposure of hepatocytes to ethanol results in agonist-selective potentiation of p42/44 mitogen-activated protein kinase (MAPK) activation, mediators of this effect of ethanol are not known. Methods: We examined the role of phosphatidylethanol (PEth), a novel phospholipid formed exclusively in the presence of ethanol. Results: PEth accumulated in primary cultures of rat hepatocytes treated with ethanol. Exogenously added PEth potentiated angiotensin II-stimulated p42/44 MAPK similarly to that observed with ethanol treatment of cells for 24 h, a condition where PEth accumulates. PEth levels remained elevated 2 h after ethanol removal subsequent to a 24-h exposure, and the potentiating effects of ethanol were also present. PEth did not potentiate p42/44 MAPK activation by either epidermal growth factor or vasopressin, thus further mimicking the known agonist selectivity for this ethanol effect. Conclusions: These results offer a novel role for PEth as a mediator in the ethanol modulation of p42/44 MAPK cascade in hepatocytes.

引用

页码：534 / 539

页数：6

共 29 条

[11] ANGIOTENSIN-II AND ACTIVE PHORBOL ESTERS INDUCE PROTOONCOGENE EXPRESSION IN ISOLATED RAT HEPATOCYTES [J].

GONZALEZESPINOSA, C ;

GARCIASAINZ, JA .

BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1136 (03) :309-314

[12]

GUSTAVSSON L, 1990, ANN NY ACAD SCI, V625, P438

[13] ETHANOL AND SIGNAL TRANSDUCTION IN THE LIVER [J].

HOEK, JB ;

THOMAS, AP ;

ROONEY, TA ;

HIGASHI, K ;

RUBIN, E .

FASEB JOURNAL, 1992, 6 (07) :2386-2396

[14]

HOEK JB, 1987, J BIOL CHEM, V262, P682

[15] Hepatic, metabolic, and nutritional disorders of alcoholism: From pathogenesis to therapy [J].

Lieber, CS .

CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES, 2000, 37 (06) :551-584

[16] PHOSPHATIDYLETHANOL AFFECTS INOSITOL 1,4,5-TRISPHOSPHATE LEVELS IN NG108-15 NEUROBLASTOMA X GLIOMA HYBRID-CELLS [J].

LUNDQVIST, C ;

RODRIGUEZ, FD ;

SIMONSSON, P ;

ALLING, C ;

GUSTAVSSON, L .

JOURNAL OF NEUROCHEMISTRY, 1993, 60 (02) :738-744

[17] Enhanced Gi-protein-mediated mitogenesis following chronic ethanol exposure in a rat model of experimental hepatocellular carcinoma [J].

McKillop, IH ;

Vyas, N ;

Schmidt, CM ;

Cahill, PA ;

Sitzmann, JV .

HEPATOLOGY, 1999, 29 (02) :412-420

[18] SYNTHESIS OF PHOSPHATIDYLETHANOL - A POTENTIAL MARKER FOR ADULT MALES AT RISK FOR ALCOHOLISM [J].

MUELLER, GC ;

FLEMING, MF ;

LEMAHIEU, MA ;

LYBRAND, GS ;

BARRY, KJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (24) :9778-9782

[19] COOMASSIE BRILLIANT BLUE STAINING OF LIPIDS ON THIN-LAYER PLATES [J].

NAKAMURA, K ;

HANDA, S .

ANALYTICAL BIOCHEMISTRY, 1984, 142 (02) :406-410

[20] ROLE OF PHOSPHATIDYLETHANOL IN MEMBRANES - EFFECTS ON MEMBRANE FLUIDITY, TOLERANCE TO ETHANOL, AND ACTIVITY OF MEMBRANE-BOUND ENZYMES [J].

OMODEOSALE, F ;

LINDI, C ;

PALESTINI, P ;

MASSERINI, M .

BIOCHEMISTRY, 1991, 30 (09) :2477-2482

← 1 2 3 →