Heme oxygenase-1 and its reaction product, carbon monoxide, prevent inflammation-related apoptotic liver damage in mice.
Standard
Heme oxygenase-1 and its reaction product, carbon monoxide, prevent inflammation-related apoptotic liver damage in mice. / Sass, Gabriele; Soares, Miguel Che Parreira; Yamashita, Kenichiro; Seyfried, Stefan; Zimmermann, Wolfram-Hubertus; Eschenhagen, Thomas; Kaczmarek, Elzbieta; Ritter, Thomas; Volk, Hans-Dieter; Tiegs, Gisa.
In: HEPATOLOGY, Vol. 38, No. 4, 4, 2003, p. 909-918.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Heme oxygenase-1 and its reaction product, carbon monoxide, prevent inflammation-related apoptotic liver damage in mice.
AU - Sass, Gabriele
AU - Soares, Miguel Che Parreira
AU - Yamashita, Kenichiro
AU - Seyfried, Stefan
AU - Zimmermann, Wolfram-Hubertus
AU - Eschenhagen, Thomas
AU - Kaczmarek, Elzbieta
AU - Ritter, Thomas
AU - Volk, Hans-Dieter
AU - Tiegs, Gisa
PY - 2003
Y1 - 2003
N2 - Heme oxygenase-1 (HO-1), a stress-responsive enzyme that catabolizes heme into carbon monoxide (CO), biliverdin, and iron, has previously been shown to protect grafts from ischemia/reperfusion injury and rejection. Here we investigated the protective potential of HO-1 in 5 models of immune-mediated liver injury. We found that up-regulation of endogenous HO-1 by cobalt-protoporphyrin-IX (CoPP) protected mice from apoptotic liver damage induced by anti-CD95 antibody (Ab) or d-galactosamine in combination with either anti-CD3 Ab, lipopolysaccharide (LPS), or tumor necrosis factor alpha (TNF-alpha). HO-1 induction prevented apoptotic liver injury, measured by inhibition of caspase 3 activation, although it did not protect mice from caspase-3-independent necrotic liver damage caused by concanavalin A (Con A) administration. In addition, overexpression of HO-1 by adenoviral gene transfer resulted in protection from apoptotic liver injury, whereas inhibition of HO-1 enzymatic activity by tin-protoporphyrin-IX (SnPP) abrogated the protective effect. HO-1-mediated protection seems to target parenchymal liver cells directly because CoPP treatment protected isolated primary hepatocytes from anti-CD95-induced apoptosis in vitro. Furthermore, depletion of Kupffer cells (KCs) did not interfere with the protective effect in vivo. Exogenous CO administration or treatment with the CO-releasing agent methylene chloride mimicked the protective effect of HO-1, whereas treatment with exogenous biliverdin or overexpression of ferritin by recombinant adenoviral gene transfer did not. In conclusion, HO-1 is a potent protective factor for cytokine- and CD95-mediated apoptotic liver damage. Induction of HO-1 might be of a therapeutic modality for inflammatory liver diseases.
AB - Heme oxygenase-1 (HO-1), a stress-responsive enzyme that catabolizes heme into carbon monoxide (CO), biliverdin, and iron, has previously been shown to protect grafts from ischemia/reperfusion injury and rejection. Here we investigated the protective potential of HO-1 in 5 models of immune-mediated liver injury. We found that up-regulation of endogenous HO-1 by cobalt-protoporphyrin-IX (CoPP) protected mice from apoptotic liver damage induced by anti-CD95 antibody (Ab) or d-galactosamine in combination with either anti-CD3 Ab, lipopolysaccharide (LPS), or tumor necrosis factor alpha (TNF-alpha). HO-1 induction prevented apoptotic liver injury, measured by inhibition of caspase 3 activation, although it did not protect mice from caspase-3-independent necrotic liver damage caused by concanavalin A (Con A) administration. In addition, overexpression of HO-1 by adenoviral gene transfer resulted in protection from apoptotic liver injury, whereas inhibition of HO-1 enzymatic activity by tin-protoporphyrin-IX (SnPP) abrogated the protective effect. HO-1-mediated protection seems to target parenchymal liver cells directly because CoPP treatment protected isolated primary hepatocytes from anti-CD95-induced apoptosis in vitro. Furthermore, depletion of Kupffer cells (KCs) did not interfere with the protective effect in vivo. Exogenous CO administration or treatment with the CO-releasing agent methylene chloride mimicked the protective effect of HO-1, whereas treatment with exogenous biliverdin or overexpression of ferritin by recombinant adenoviral gene transfer did not. In conclusion, HO-1 is a potent protective factor for cytokine- and CD95-mediated apoptotic liver damage. Induction of HO-1 might be of a therapeutic modality for inflammatory liver diseases.
KW - Animals
KW - Mice
KW - Mice, Inbred BALB C
KW - Gene Therapy
KW - Apoptosis
KW - Liver/pathology
KW - Membrane Proteins
KW - Heme Oxygenase-1
KW - Carbon Monoxide/pharmacology
KW - Adenoviridae/genetics
KW - Enzyme Induction
KW - Heme Oxygenase (Decyclizing)/physiology
KW - Hepatocytes/enzymology
KW - Inflammation/pathology
KW - Animals
KW - Mice
KW - Mice, Inbred BALB C
KW - Gene Therapy
KW - Apoptosis
KW - Liver/pathology
KW - Membrane Proteins
KW - Heme Oxygenase-1
KW - Carbon Monoxide/pharmacology
KW - Adenoviridae/genetics
KW - Enzyme Induction
KW - Heme Oxygenase (Decyclizing)/physiology
KW - Hepatocytes/enzymology
KW - Inflammation/pathology
M3 - SCORING: Journal article
VL - 38
SP - 909
EP - 918
JO - HEPATOLOGY
JF - HEPATOLOGY
SN - 0270-9139
IS - 4
M1 - 4
ER -
