Increased heme oxygenase-1 gene expression in liver cells and splanchnic organs from portal hypertensive rats.
Heme oxygenase (HO) catalyzes the conversion of heme into biliverdin, iron, and carbon monoxide (CO). Two isoforms of HO 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 (PH) and sham-operated (SO) rats. Liver cells (hepatocytes, Kupffer and stellate cells), 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-1 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.
Fernandez
M
M
Division of Digestive Disease and Nutrition and The Liver, Biliary, Pancreatic Center, UMass Memorial Health Care, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Bonkovsky
H L
HL
D000818:Animals; D003106:Colon / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006975:Hypertension, Portal / Q000201:enzymology* / Q000235:genetics; D007422:Intestines / Q000201:enzymology; D007728:Kupffer Cells / Q000201:enzymology; D008099:Liver / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008643:Mesentery / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000201:enzymology; D014158:Transcription, Genetic
D012333:RNA, Messenger; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2