TY - JOUR
T1 - Altered expression of heme oxygenase-1 in the livers of patients with portal hypertensive diseases
AU - Makino, Nobuya
AU - Suematsu, Makoto
AU - Sugiura, Yoshiaki
AU - Morikawa, Hiroyasu
AU - Shiomi, Susumu
AU - Goda, Nobuhito
AU - Sano, Tsuyoshi
AU - Nimura, Yuji
AU - Sugimachi, Keizo
AU - Ishimura, Yuzuru
N1 - Funding Information:
Abbreviations: HO, heme oxygenase; IPH, idiopathic portal hypertension; MoAb, monoclonal antibody; PBS, phosphate-buffered saline; α-SMA, α-smooth muscle actin. From the Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan; 2Department of Surgery II, National Defense Medical College, Tokorozawa, Saitama, Japan; 3Third Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan; 4First Department of Surgery, Nagoya University School of Medicine, Nagoya, Japan; and 5Second Department of Surgery, Kyushu University School of Medicine, Fukuoka, Japan. Received May 15, 2000; accepted October 20, 2000. Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan, and by grants from Surveys and Research on Specific Diseases from the Ministry of Health, and by Keio University Medical Science Fund. Address reprint requests to: Yuzuru Ishimura, M.D., Ph.D., Professor and Chair, Department of Biochemistry, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail: yishimur@med.keio.ac.jp; fax: 81-3-3358-8138. Copyright © 2001 by the American Association for the Study of Liver Diseases. 0270-9139/01/3301-0007$3.00/0 doi:10.1053/jhep.2001.21161
PY - 2001
Y1 - 2001
N2 - This study was designed to determine changes in expression of heme oxygenase (HO)-1, the stress-inducible and carbon monoxide-producing enzyme, in normotensive and portal hypertensive human livers. GTS-1, a monoclonal antibody against rat HO-1 cross-reacted with the human HO-1 and blocked its enzyme activity, allowing us to examine the activity and localization of HO-1. In controls, approximately 50% of the total HO activity was from HO-1 as judged by the sensitivity to GTS-1, while the rest of activity was from other isozymes such as HO-2, HO-1 was expressed mainly in a subpopulation of Kupffer cells, and the expression in hepatic stellate cells, sinusoidal endothelial cells, and hepatocytes was little, if any. The HO-1 expression exhibited quite different pictures in the livers of portal hypertensive diseases. In cirrhotic livers, which undergo portal hypertension through increases in intrasinusoidal resistance and regenerative changes in the parenchyma, HO-1 occurred in a majority of Kupffer cells and was also observed in hepatocytes. Consequently, the total HO-1 activities became significantly greater in these tissues than those from normal individuals. By contrast, livers of idiopathic portal hypertension that are characterized by an increase in presinusoidal resistance displayed a significant decrease in the HO-1 expression in Kupffer cells, and its hepatocellular expression was not detectable. Although factors involved in altered HO-1 expression in these cells remain unknown, the results suggest that Kupffer cells could alter their expression of HO-1 in response to local hemodynamic changes associated with chronic portal hypertension in humans.
AB - This study was designed to determine changes in expression of heme oxygenase (HO)-1, the stress-inducible and carbon monoxide-producing enzyme, in normotensive and portal hypertensive human livers. GTS-1, a monoclonal antibody against rat HO-1 cross-reacted with the human HO-1 and blocked its enzyme activity, allowing us to examine the activity and localization of HO-1. In controls, approximately 50% of the total HO activity was from HO-1 as judged by the sensitivity to GTS-1, while the rest of activity was from other isozymes such as HO-2, HO-1 was expressed mainly in a subpopulation of Kupffer cells, and the expression in hepatic stellate cells, sinusoidal endothelial cells, and hepatocytes was little, if any. The HO-1 expression exhibited quite different pictures in the livers of portal hypertensive diseases. In cirrhotic livers, which undergo portal hypertension through increases in intrasinusoidal resistance and regenerative changes in the parenchyma, HO-1 occurred in a majority of Kupffer cells and was also observed in hepatocytes. Consequently, the total HO-1 activities became significantly greater in these tissues than those from normal individuals. By contrast, livers of idiopathic portal hypertension that are characterized by an increase in presinusoidal resistance displayed a significant decrease in the HO-1 expression in Kupffer cells, and its hepatocellular expression was not detectable. Although factors involved in altered HO-1 expression in these cells remain unknown, the results suggest that Kupffer cells could alter their expression of HO-1 in response to local hemodynamic changes associated with chronic portal hypertension in humans.
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U2 - 10.1053/jhep.2001.21161
DO - 10.1053/jhep.2001.21161
M3 - Article
C2 - 11124818
AN - SCOPUS:0035196917
SN - 0270-9139
VL - 33
SP - 32
EP - 42
JO - Hepatology
JF - Hepatology
IS - 1
ER -