Increased heme oxygenase-1 gene expression in liver cells and splanchnic organs from portal hypertensive rats

被引:87
作者
Fernandez, M
Bonkovsky, HL
机构
[1] Univ Massachusetts, Sch Med, Dept Med, Div Digest Dis & Nutr, Worcester, MA 01655 USA
[2] Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Worcester, MA 01655 USA
[3] UMass Mem Hlth Care, Liver Biliary Pancreat Ctr, Worcester, MA USA
[4] UMass Mem Hlth Care, Div Digest Dis & Nutr, Worcester, MA USA
关键词
D O I
10.1002/hep.510290621
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Heme oxygenase (HO) catalyzes the conversion of heme into biliverdin, iron, and carbon monoxide (CO). Two isoforms of WO have been identified: the inducible HO-1 and the constitutive HO-2. CO, like nitric oxide, is an endogenous vasodilator that could contribute to modulation of systemic and local vascular tone. The aim of the present study was to determine the expression of HO isoforms in liver cells and splanchnic organs from portal hypertensive (PPI) and sham-operated (SO) rats. Liver cells (hepatocytes, Kupffer and stellate tells), and splanchnic organs (liver, mesentery, intestine, colon, and spleen) were isolated From PH and SO rats. Expression of HO mRNA and protein was assessed by reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. In SO rats, HO-1 mRNA expression was only detected in spleen. In contrast, in PH rats, HO-1 mRNA was expressed in hepatocytes, Kupffer cells, and in all the splanchnic organs studied. Moreover, levels of HO-1 protein in splanchnic organs were significantly higher in PH rats than in SO animals. In addition, HO-2 expression was observed in all liver cell types and splanchnic organs studied from both PH and SO rats. These results indicate that HO-2 is expressed in parenchymal and nonparenchymal liver cells, as well as splanchnic organs, of both PH and SO rats. In addition, HO-I is up-regulated in hepatocytes and splanchnic organs of PH rats, compared with SO animals, suggesting a possible pathophysiological role of HO-1 in chronic portal hypertension.
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页码:1672 / 1679
页数:8
相关论文
共 58 条
[1]   METABOLIC REGULATION OF HEME CATABOLISM AND BILIRUBIN PRODUCTION .1. HORMONAL-CONTROL OF HEPATIC HEME OXYGENASE ACTIVITY [J].
BAKKEN, AF ;
SCHMID, R ;
THALER, MM .
JOURNAL OF CLINICAL INVESTIGATION, 1972, 51 (03) :530-&
[2]   Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liver [J].
Bauer, I ;
Wanner, GA ;
Rensing, H ;
Alte, G ;
Miescher, EA ;
Wolf, B ;
Pannen, BHJ ;
Clemens, MG ;
Bauer, M .
HEPATOLOGY, 1998, 27 (03) :829-838
[3]   Evidence for a functional link between stress response and vascular control in hepatic portal circulation [J].
Bauer, M ;
Pannen, BHJ ;
Bauer, I ;
Herzog, C ;
Wanner, GA ;
Hanselmann, R ;
Zhang, JX ;
Clemens, MG ;
Larsen, R .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 1996, 271 (05) :G929-G935
[4]   HEMOGLOBIN AND ERYTHROCYTE CATABOLISM IN RAT-LIVER - SEPARATE ROLES OF PARENCHYMAL AND SINUSOIDAL CELLS [J].
BISSELL, DM ;
SCHMID, R ;
HAMMAKER, L .
BLOOD-THE JOURNAL OF HEMATOLOGY, 1972, 40 (06) :812-+
[5]   Induction of HSP 32 gene in hypoxic cardiomyocytes is attenuated by treatment with N-acetyl-L-cysteine [J].
Borger, DR ;
Essig, DA .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1998, 274 (03) :H965-H973
[6]  
BOSCH J, 1992, GASTROENTEROL CLIN N, V21, P1
[7]  
BRUNE B, 1987, MOL PHARMACOL, V32, P497
[8]   Increased endothelial nitric oxide synthase activity in the hyperemic vessels of portal hypertensive rats [J].
Cahill, PA ;
Redmond, EM ;
Hodges, R ;
Zhang, SM ;
Sitzmann, JV .
JOURNAL OF HEPATOLOGY, 1996, 25 (03) :370-378
[9]   VASCULAR SMOOTH-MUSCLE CELL HEME OXYGENASES GENERATE GUANYLYL CYCLASE STIMULATORY CARBON-MONOXIDE [J].
CHRISTODOULIDES, N ;
DURANTE, W ;
KROLL, MH ;
SCHAFER, AI .
CIRCULATION, 1995, 91 (09) :2306-2309
[10]   Remodeling of hepatic microvascular responsiveness after ischemia/reperfusion [J].
Clemens, MG ;
Bauer, M ;
Pannen, BHJ ;
Bauer, I ;
Zhang, JX .
SHOCK, 1997, 8 (02) :80-85