HO-1 Overexpression Attenuates Endotoxin Effects on CAT-2 Isozymes Expression

Huang, Te‐Yang; Tsai, Pei Shan; Huang, Chun Jen

doi:10.1016/j.jss.2007.06.027

Cited by 5 publications

(3 citation statements)

References 21 publications

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“…In addition, although BDL progressively increased inducible nitric oxide synthase (iNOS) mRNA expression in both genotypes, compared with sham controls (at least, P <0.05), BDL RIP3 −/− mice displayed reduced mRNA levels of iNOS compared with BDL WT mice ( P <0.05; Figure 5b ), consistent with the notion that HO-1 attenuates the expression of iNOS. 26 , 27 , 28 Quantification of labile iron and the Perls' Prussian Blue staining also showed that deletion of RIP3 significantly increased iron deposition in livers from mice post-BDL at both time-points (at least, P <0.05; Figure 5c ). Reflecting iron accumulation, BDL RIP3 −/− mice displayed increased hepatic expression of hepcidin, ferritin heavy chain (FtH) and ferritin light chain (FtL) (at least, P <0.05; Figure 5d ).…”

Section: Resultsmentioning

confidence: 85%

Activation of necroptosis in human and experimental cholestasis

et al. 2016

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Cholestasis encompasses liver injury and inflammation. Necroptosis, a necrotic cell death pathway regulated by receptor-interacting protein (RIP) 3, may mediate cell death and inflammation in the liver. We aimed to investigate the role of necroptosis in mediating deleterious processes associated with cholestatic liver disease. Hallmarks of necroptosis were evaluated in liver biopsies of primary biliary cholangitis (PBC) patients and in wild-type and RIP3-deficient (RIP3−/−) mice subjected to common bile duct ligation (BDL). The functional link between RIP3, heme oxygenase-1 (HO-1) and antioxidant response was investigated in vivo after BDL and in vitro. We demonstrate increased RIP3 expression and mixed lineage kinase domain-like protein (MLKL) phosphorylation in liver samples of human PBC patients, coincident with thioflavin T labeling, suggesting activation of necroptosis. BDL resulted in evident hallmarks of necroptosis, concomitant with progressive bile duct hyperplasia, multifocal necrosis, fibrosis and inflammation. MLKL phosphorylation was increased and insoluble aggregates of RIP3, MLKL and RIP1 formed in BLD liver tissue samples. Furthermore, RIP3 deficiency blocked BDL-induced necroinflammation at 3 and 14 days post-BDL. Serum hepatic enzymes, fibrogenic liver gene expression and oxidative stress decreased in RIP3−/− mice at 3 days after BDL. However, at 14 days, cholestasis aggravated and fibrosis was not halted. RIP3 deficiency further associated with increased hepatic expression of HO-1 and accumulation of iron in BDL mice. The functional link between HO-1 activity and bile acid toxicity was established in RIP3-deficient primary hepatocytes. Necroptosis is triggered in PBC patients and mediates hepatic necroinflammation in BDL-induced acute cholestasis. Targeting necroptosis may represent a therapeutic strategy for acute cholestasis, although complementary approaches may be required to control progression of chronic cholestatic liver disease.

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Section: Resultsmentioning

confidence: 85%

Activation of necroptosis in human and experimental cholestasis

et al. 2016

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“…HO-1 expression attenuates the endotoxin-induced expression of iNOS and cationic amino acid transporter (CAT-2) isozymes in septic rat and thus reduces increases in NO production and L-arginine transport (Huang et al 2008).…”

Section: Heme Oxygenase-1 and Inflammationmentioning

confidence: 99%

Protective role of heme oxygenase-1 in liver

2012

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Heme oxygenase-1 (HO-1) is the rate limiting enzyme in heme catabolism and degrades heme to carbon monoxide, biliverdin, and ferrous iron. HO-1 transcriptional induction occurs in response to multiple forms of chemical, physical stress and cytokines. HO-1 confers cytoprotection by inhibiting apoptosis, oxidative stress, and inflammation. Hepatitis C virus (HCV) is a major cause of cirrhosis and hepatocellular carcinoma. It has been shown that HO-1 induction and HO-1 products interfere with replication of HCV and markedly decreased HCV replication. However, a growing body of evidence indicates that induction of HO-1 may be involved in carcinogenesis and can play a role in the metastasis and growth of tumors. The antioxidant, antiviral activity of HO-1 makes it the cytoprotective enzyme for liver tissue in HCV infection, and induction of HO-1 can be suggested as a future therapeutic approach. However, the role of HO-1 in tumor growth should not be ignored.

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“…3 It also inhibits nitric oxide production in endotoxic shock. 4 On the other hand, inhibition of Heme oxygenase-1 function has a potent anticarcinogenic influence. For instance, knockdown of Heme oxygenase-1 function by small interfering RNAs has a negative effect on tumor growth in malignancies such as hepatocellular carcinomas.…”

mentioning

confidence: 99%

Beyond hepatitis C

Kapoor¹

2009

Hepatology

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HO-1 Overexpression Attenuates Endotoxin Effects on CAT-2 Isozymes Expression

Cited by 5 publications

References 21 publications

Activation of necroptosis in human and experimental cholestasis

Activation of necroptosis in human and experimental cholestasis

Protective role of heme oxygenase-1 in liver

Beyond hepatitis C

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