Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene

Hayashi, Shunsuke; Omata, Yoshiaki; Sakamoto, Hiroshi; Higashimoto, Yuichiro; Hara, Takayuki; Sagara, Yusuke; Noguchi, Masato

doi:10.1016/j.gene.2004.04.002

Cited by 204 publications

(148 citation statements)

References 12 publications

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“…Of the isoforms of HO identified, HO-1 is highly inducible, whereas HO-2 is constitutively expressed. HO-3 is the least understood and may be a pseudogene, and at least in the rat, it has been suggested that there is no functional HO-3 gene (12). HO-1 can be induced by a variety of agents causing oxidative stress including heavy metals, cytokines, hormones, endotoxin, and heat shock (1,3,6,17,25).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of low-dose carbon monoxide against renal fibrosis induced by unilateral ureteral obstruction

Wang¹,

Lee²,

Kwak³

et al. 2008

American Journal of Physiology-Renal Physiology

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Tubulointerstitial fibrosis is a hallmark of chronic progressive kidney disease leading to end-stage renal failure. An endogenous product of heme oxygenase activity, carbon monoxide (CO), has been shown to exert cytoprotection against tissue injury. Here, we explored the effects of exogenous administration of low-dose CO in an in vivo model of renal fibrosis induced by unilateral ureteral obstruction (UUO) and examined whether CO can protect against kidney injury. UUO in mice leads to increased extracellular matrix (ECM) deposition and tubulointerstitial fibrosis within 4 to 7 days. Kidneys of mice exposed to low-dose CO, however, had markedly reduced ECM deposition after UUO. Moreover, low-dose CO treatment inhibited the induction of α-smooth muscle actin (α-SMA) and major ECM proteins, type 1 collagen and fibronectin, in kidneys after UUO. In contrast, these anti-fibrotic effects of CO treatment were abrogated in mice carrying null mutation of Mkk3, suggesting involvement of the MKK3 signaling pathway in mediating the CO effects. Additionally, in vitro CO exposure markedly inhibited TGF-β1-induced expression of α-SMA, collagen, and fibronectin in renal proximal tubular epithelial cells. Our findings suggest that low-dose CO exerts protective effects, via the MKK3 pathway, to inhibit development of renal fibrosis in obstructive nephropathy.

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Section: Discussionmentioning

confidence: 99%

Protective effects of low-dose carbon monoxide against renal fibrosis induced by unilateral ureteral obstruction

Wang¹,

Lee²,

Kwak³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…In mammals, two heme oxygenase (HO) enzymes, HO-1 and HO-2, have been identified, confirmed and characterized [123,151,152]. A third gene, HO-3, appears to be a pseudogene derived from HO-2 [153]. HOs are the rate-limiting enzymes in heme degradation.…”

Section: The Oxidant Potential Of Heme Is Neutralized By Multiple Hemmentioning

confidence: 99%

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

2006

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“…However, recent work suggests that HO-3 may be a pseudogene derived from HO-2 transcripts (4). The HO-2 isoform is constitutively expressed and is present in high concentrations in the brain and testes (5). In contrast, HO-1 is ubiquitously distributed and strongly induced by oxidative, nitrosative, osmotic, and hemodynamic stress (6 -10).…”

mentioning

confidence: 99%

Endoplasmic Reticulum Stress Stimulates Heme Oxygenase-1 Gene Expression in Vascular Smooth Muscle

Liu¹,

Peyton²,

Ensenat³

et al. 2005

Journal of Biological Chemistry

116

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Heme oxygenase-1 (HO-1) is a cytoprotective protein that catalyzes the degradation of heme to biliverdin, iron, and carbon monoxide (CO). In the present study, we found that endoplasmic reticulum (ER) stress induced by a variety of experimental agents stimulated a time-and concentration-dependent increase in HO-1 mRNA and protein in vascular smooth muscle cells (SMC). The induction of HO-1 by ER stress was blocked by actinomycin D or cycloheximide and was independent of any changes in HO-1 mRNA stability. Luciferase reporter assays indicated that ER stress stimulated HO-1 promoter activity via the antioxidant response element. Moreover, ER stress induced the nuclear import of Nrf2 and the binding of Nrf2 to the HO-1 antioxidant response element. Interestingly, ER stress stimulated SMC apoptosis, as demonstrated by annexin V binding, caspase-3 activation, and DNA laddering. The induction of apoptosis by ER stress was potentiated by HO inhibition, whereas it was prevented by addition of HO substrate. In addition, exposure of SMC to exogenously administered CO inhibited ER stress-mediated apoptosis, and this was associated with a decrease in the expression of the proapoptotic protein, GADD153. In contrast, the other HO-1 products failed to block apoptosis or GADD153 expression during ER stress. These results demonstrated that ER stress is an inducer of HO-1 gene expression in vascular SMC and that HO-1-derived CO acts in an autocrine fashion to inhibit SMC apoptosis. The capacity of ER stress to stimulate the HO-1/CO system provides a novel mechanism by which this organelle regulates cell survival.

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Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene

Cited by 204 publications

References 12 publications

Protective effects of low-dose carbon monoxide against renal fibrosis induced by unilateral ureteral obstruction

Protective effects of low-dose carbon monoxide against renal fibrosis induced by unilateral ureteral obstruction

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

Endoplasmic Reticulum Stress Stimulates Heme Oxygenase-1 Gene Expression in Vascular Smooth Muscle

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