Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proliferation of hepatic stellate cells (HSCs) is central for the development of fibrosis during liver injury. We have shown previously that butein (3,4,2',4'-tetrahydroxychalcone) suppresses myofibroblastic differentiation of rat HSCs. Our aim in this study was to determine whether a new synthetic chalcone derivative, 2',4',6'-tris(methoxymethoxy) chalcone (TMMC) inhibits HSC proliferation induced by serum- or platelet-derived growth factor (PDGF). TMMC significantly inhibited growth factor-induced HSC proliferation. The inhibition of PDGF-induced proliferation by TMMC was associated with the phosphatidylinositol 3-kinase-Akt-p70(S6K) pathways. TMMC induced the expression of heme oxygenase 1 (HO-1) in HSCs. Using the chemical inhibitor tin protoporphyrin, we also found that the inhibitory action of TMMC on PDGF-induced proliferation is mediated by HO-1. Glutathione (GSH) depletion produced by TMMC activated extracellular signal-regulated kinase (ERK), which led to c-Fos expression and transactivation of activator protein 1 (AP-1) and HO-1 gene expression in the HSCs. These results demonstrate that TMMC preferentially activates ERK and that this activation leads to the transcriptional activation of AP-1 and consequently to HO-1 expression. HO-1 expression might be responsible for the antiproliferative effect of TMMC on HSCs.
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PMID:2',4',6'-Tris(methoxymethoxy) chalcone attenuates hepatic stellate cell proliferation by a heme oxygenase-dependent pathway. 1698 36

We evaluated whether the antiproliferative effects of isoliquiritigenin (ISL) on rat hepatic stellate cells (HSCs) are related to the induction of heme oxygenase 1 (HO-1) expression. ISL significantly inhibited serum- or growth factor-induced HSC proliferation. The inhibition of platelet-derived growth factor (PDGF)-induced proliferation by ISL was associated with the mitogen-activated protein kinase and phosphatidylinositol 3-kinase-Akt-p70 (S6K) pathways. ISL induced the expression of HO-1 in HSCs. Using the chemical inhibitor tin protoporphyrin, we also found that the inhibitory action of ISL on PDGF-induced proliferation is mediated by HO-1. These data suggest that HO-1 expression is responsible for the antiproliferative effect of ISL on HSCs.
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PMID:Isoliquiritigenin inhibits cell proliferation by a heme oxygenase-dependent pathway in rat hepatic stellate cells. 1856 66