Title : How Heme Oxygenase-1 Prevents Heme-Induced Cell Death.

Pub. Date : 2015

PMID : 26270345






11 Functional Relationships(s)
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Protein Name
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1 Earlier observations indicate that free heme is selectively toxic to cells lacking heme oxygenase-1 (HO-1) but how this enzyme prevents heme toxicity remains unexplained. Heme heme oxygenase 1 Homo sapiens
2 Earlier observations indicate that free heme is selectively toxic to cells lacking heme oxygenase-1 (HO-1) but how this enzyme prevents heme toxicity remains unexplained. Heme heme oxygenase 1 Homo sapiens
3 Here, using A549 (human lung cancer) and immortalized human bronchial epithelial cells incubated with exogenous heme, we find knock-down of HO-1 using siRNA does promote the accumulation of cell-associated heme and heme-induced cell death. Heme heme oxygenase 1 Homo sapiens
4 Here, using A549 (human lung cancer) and immortalized human bronchial epithelial cells incubated with exogenous heme, we find knock-down of HO-1 using siRNA does promote the accumulation of cell-associated heme and heme-induced cell death. Heme heme oxygenase 1 Homo sapiens
5 Here, using A549 (human lung cancer) and immortalized human bronchial epithelial cells incubated with exogenous heme, we find knock-down of HO-1 using siRNA does promote the accumulation of cell-associated heme and heme-induced cell death. Heme heme oxygenase 1 Homo sapiens
6 However, it appears that the toxic effects of heme are exerted by "loose" (probably intralysosomal) iron because cytotoxic effects of heme are lessened by pre-incubation of HO-1 deficient cells with desferrioxamine (which localizes preferentially in the lysosomal compartment). Heme heme oxygenase 1 Homo sapiens
7 However, it appears that the toxic effects of heme are exerted by "loose" (probably intralysosomal) iron because cytotoxic effects of heme are lessened by pre-incubation of HO-1 deficient cells with desferrioxamine (which localizes preferentially in the lysosomal compartment). Heme heme oxygenase 1 Homo sapiens
8 Supporting the importance of endogenous oxidant production, both chemical and siRNA inhibition of catalase activity predisposes HO-1 deficient cells to heme-mediated killing. Heme heme oxygenase 1 Homo sapiens
9 Importantly, it appears that HO-1 deficiency somehow blocks the induction of ferritin; control cells exposed to heme show ~10-fold increases in ferritin heavy chain expression whereas in heme-exposed HO-1 deficient cells ferritin expression is unchanged. Heme heme oxygenase 1 Homo sapiens
10 Importantly, it appears that HO-1 deficiency somehow blocks the induction of ferritin; control cells exposed to heme show ~10-fold increases in ferritin heavy chain expression whereas in heme-exposed HO-1 deficient cells ferritin expression is unchanged. Heme heme oxygenase 1 Homo sapiens
11 Finally, overexpression of ferritin H chain in HO-1 deficient cells completely prevents heme-induced cytotoxicity. Heme heme oxygenase 1 Homo sapiens