Ferritin heavy chain mediates the protective effect of heme oxygenase-1 against oxidative stress

Hui Teng Cheng; Chung Jen Yen; Chen Chih Chang; Kuo Tong Huang; Kuo Hsuan Chen; Rui Yang Zhang; Ping Yi Lee; Shi Chuen Miaw; Jenq Wen Huang; Chih Kang Chiang; Kwan Dun Wu; Kuan Yu Hung

doi:10.1016/j.bbagen.2015.09.018

Ferritin heavy chain mediates the protective effect of heme oxygenase-1 against oxidative stress

Hui Teng Cheng, Chung Jen Yen, Chen Chih Chang, Kuo Tong Huang, Kuo Hsuan Chen, Rui Yang Zhang, Ping Yi Lee, Shi Chuen Miaw, Jenq Wen Huang, Chih Kang Chiang, Kwan Dun Wu, Kuan Yu Hung

Research output: Contribution to journal › Article › peer-review

49 Citations (Scopus)

Abstract

The phenomenon that heme oxygenase-1 (HO-1) protects cell from injury yet its enzymatic product, iron, may facilitate generation of free radical has been long puzzling. Here we establish a functional connection between ferritin heavy chain (FHC) and HO-1. In human lupus nephritis HO-1 and FHC are colocalizedwithin the glomeruli. In rodent anti-Thy1 (thymocyte antigen 1) induced glomerulonephritis, hemeoxygenase blockade lowers the expression of FHC and accelerates mesangial cell death. Stimulation of heme oxygenase in cultured rat mesangial cell enhances its resistance to hydrogen peroxide, whereas FHC knockdown by RNA interference compromises this salutary effect. RNA interference of HO-1 makes the cell more susceptible to hydrogen peroxide, which can be rescued by forced expression of wild-type FHC but not mutants that lose the capacity of iron storage and ferroxidase activity. Phosphorylation of JunD was not sustained in these cells. Microarray analysis identifies four candidate transcriptional factors tha may regulate the HO-1-induced transcription of FHC. Our results support the role of FHC in neutralizing the iron toxicity as well as mediating the protective effect of HO-1 in response to oxidative stress.

Original language	English
Pages (from-to)	2506-2517
Number of pages	12
Journal	Biochimica et Biophysica Acta - General Subjects
Volume	1850
Issue number	12
DOIs	https://doi.org/10.1016/j.bbagen.2015.09.018
Publication status	Published - Dec 1 2015
Externally published	Yes

Keywords

Ferritin heavy chain
Heme oxygenase-1
Inflammation
Oxidative stress

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

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10.1016/j.bbagen.2015.09.018

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Cheng, H. T., Yen, C. J., Chang, C. C., Huang, K. T., Chen, K. H., Zhang, R. Y., Lee, P. Y., Miaw, S. C., Huang, J. W., Chiang, C. K., Wu, K. D., & Hung, K. Y. (2015). Ferritin heavy chain mediates the protective effect of heme oxygenase-1 against oxidative stress. Biochimica et Biophysica Acta - General Subjects, 1850(12), 2506-2517. https://doi.org/10.1016/j.bbagen.2015.09.018

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title = "Ferritin heavy chain mediates the protective effect of heme oxygenase-1 against oxidative stress",

abstract = "The phenomenon that heme oxygenase-1 (HO-1) protects cell from injury yet its enzymatic product, iron, may facilitate generation of free radical has been long puzzling. Here we establish a functional connection between ferritin heavy chain (FHC) and HO-1. In human lupus nephritis HO-1 and FHC are colocalizedwithin the glomeruli. In rodent anti-Thy1 (thymocyte antigen 1) induced glomerulonephritis, hemeoxygenase blockade lowers the expression of FHC and accelerates mesangial cell death. Stimulation of heme oxygenase in cultured rat mesangial cell enhances its resistance to hydrogen peroxide, whereas FHC knockdown by RNA interference compromises this salutary effect. RNA interference of HO-1 makes the cell more susceptible to hydrogen peroxide, which can be rescued by forced expression of wild-type FHC but not mutants that lose the capacity of iron storage and ferroxidase activity. Phosphorylation of JunD was not sustained in these cells. Microarray analysis identifies four candidate transcriptional factors tha may regulate the HO-1-induced transcription of FHC. Our results support the role of FHC in neutralizing the iron toxicity as well as mediating the protective effect of HO-1 in response to oxidative stress.",

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author = "Cheng, {Hui Teng} and Yen, {Chung Jen} and Chang, {Chen Chih} and Huang, {Kuo Tong} and Chen, {Kuo Hsuan} and Zhang, {Rui Yang} and Lee, {Ping Yi} and Miaw, {Shi Chuen} and Huang, {Jenq Wen} and Chiang, {Chih Kang} and Wu, {Kwan Dun} and Hung, {Kuan Yu}",

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AU - Cheng, Hui Teng

AU - Yen, Chung Jen

AU - Chang, Chen Chih

AU - Huang, Kuo Tong

AU - Chen, Kuo Hsuan

AU - Zhang, Rui Yang

AU - Lee, Ping Yi

AU - Miaw, Shi Chuen

AU - Huang, Jenq Wen

AU - Chiang, Chih Kang

AU - Wu, Kwan Dun

AU - Hung, Kuan Yu

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N2 - The phenomenon that heme oxygenase-1 (HO-1) protects cell from injury yet its enzymatic product, iron, may facilitate generation of free radical has been long puzzling. Here we establish a functional connection between ferritin heavy chain (FHC) and HO-1. In human lupus nephritis HO-1 and FHC are colocalizedwithin the glomeruli. In rodent anti-Thy1 (thymocyte antigen 1) induced glomerulonephritis, hemeoxygenase blockade lowers the expression of FHC and accelerates mesangial cell death. Stimulation of heme oxygenase in cultured rat mesangial cell enhances its resistance to hydrogen peroxide, whereas FHC knockdown by RNA interference compromises this salutary effect. RNA interference of HO-1 makes the cell more susceptible to hydrogen peroxide, which can be rescued by forced expression of wild-type FHC but not mutants that lose the capacity of iron storage and ferroxidase activity. Phosphorylation of JunD was not sustained in these cells. Microarray analysis identifies four candidate transcriptional factors tha may regulate the HO-1-induced transcription of FHC. Our results support the role of FHC in neutralizing the iron toxicity as well as mediating the protective effect of HO-1 in response to oxidative stress.

AB - The phenomenon that heme oxygenase-1 (HO-1) protects cell from injury yet its enzymatic product, iron, may facilitate generation of free radical has been long puzzling. Here we establish a functional connection between ferritin heavy chain (FHC) and HO-1. In human lupus nephritis HO-1 and FHC are colocalizedwithin the glomeruli. In rodent anti-Thy1 (thymocyte antigen 1) induced glomerulonephritis, hemeoxygenase blockade lowers the expression of FHC and accelerates mesangial cell death. Stimulation of heme oxygenase in cultured rat mesangial cell enhances its resistance to hydrogen peroxide, whereas FHC knockdown by RNA interference compromises this salutary effect. RNA interference of HO-1 makes the cell more susceptible to hydrogen peroxide, which can be rescued by forced expression of wild-type FHC but not mutants that lose the capacity of iron storage and ferroxidase activity. Phosphorylation of JunD was not sustained in these cells. Microarray analysis identifies four candidate transcriptional factors tha may regulate the HO-1-induced transcription of FHC. Our results support the role of FHC in neutralizing the iron toxicity as well as mediating the protective effect of HO-1 in response to oxidative stress.

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KW - Oxidative stress

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Ferritin heavy chain mediates the protective effect of heme oxygenase-1 against oxidative stress

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