PMID:22989377

Citation	'Lanceta, L, Li, C, Choi, AM and Eaton, JW (2012) Heme oxygenase-1 overexpression alters intracellular iron distribution. Biochem. J. '
Abstract	Induction or ectopic overexpression of heme oxygenase 1 (HO-1) protects against a wide variety of disorders. These protective effects have been variably ascribed to generation of carbon monoxide (released during cleavage of the alpha methene bridge of heme) and/or to production of the antioxidant, bilirubin. We have investigated HO-1 overexpressing A549 cells and find that, as expected, HO-1 overexpressing cells are resistant to killing by hydrogen peroxide. Surprisingly, these cells have ~2x the normal amount of intracellular iron which usually tends to amplify oxidant killing. However, HO-1 overexpressing cells contain only ~25% as much 'loose' (probably redox active) iron. Indeed, inhibition of ferritin synthesis (via siRNA directed at the ferritin heavy chain) sensitizes the HO-1 overexpressing cells to peroxide killing. It appears that HO-1 overexpression leads to enhanced destruction of heme, consequent 2-3 fold induction of ferritin, and compensatory increases in transferrin receptor expression and heme synthesis. However, there is no functional heme deficiency because cellular oxygen consumption and catalase activity are similar in both cell types. We conclude that, at least in many cases, the cytoprotective effects of HO-1 induction or forced overexpression may derive from elevated expression of ferritin and consequent reduction of redox active 'loose' iron.
Links	PubMed Online version:10.1042/BJ20120936
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:HMOX1		GO:0042542: response to hydrogen peroxide	ECO:0000315:		P		Figure 1 shows overexpression of HO1 leads to less loss of viability due to H2O2 treatment.	complete CACAO 5572
HUMAN:HMOX1	involved_in	GO:0006879: cellular iron ion homeostasis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:HMOX1		GO:0006879: cellular iron ion homeostasis	ECO:0000315:		P		Figure 2B shows overexpression of HO1 leads to increased bound intracellular iron.	complete CACAO 5573
RAT:HMOX1		GO:1901299: negative regulation of hydrogen peroxide-mediated programmed cell death	ECO:0000314:		P		Figure 1 shows that cells overexpressing HO-1 are protected against peroxide killing	complete CACAO 5914

References

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