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Integrative survival response evoked by heme oxygenase-1 and heme metabolites.

Pae HO, Kim EC, Chung HT - J Clin Biochem Nutr (2008)

Bottom Line: The mechanism of protective actions of HO-1 has not been completely elucidated, but recent evidence suggests that one or more of heme metabolites can mediate the protective effects of HO-1.Many of these effects of CO depend on the production of cyclic guanosine monophosphate (cGMP), and the modulation of mitogen-activated protein kinase (MAPK) pathways.In addition, the cytoprotective roles of HO-1 shall be discussed from the perspective of each of the metabolic by-products.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.

ABSTRACT
Heme oxygenase (HO) catalyzes the rate-limiting step in heme degradation to produce carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently converted to bilirubin by its reductase, and iron is recycled for heme synthesis. The inducible HO isoform, HO-1, is involved in the protection of multiple tissues and organs. The mechanism of protective actions of HO-1 has not been completely elucidated, but recent evidence suggests that one or more of heme metabolites can mediate the protective effects of HO-1. Particularly, CO mimics the antioxidant, anti-inflammatory, anti-apoptotic and antiproliferative actions of HO-1. Many of these effects of CO depend on the production of cyclic guanosine monophosphate (cGMP), and the modulation of mitogen-activated protein kinase (MAPK) pathways. The transcription factors, including nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases, including MAPK pathway, play an important regulatory role in HO-1 expression by dietary antioxidants and drugs. This review attempts to concisely summarize the molecular and biochemical characteristics of HO-1, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by dietary antioxidants and drugs. In addition, the cytoprotective roles of HO-1 shall be discussed from the perspective of each of the metabolic by-products.

No MeSH data available.


Signaling pathways leading to HO-1 expression by phytochemicals and drugs through MAPK-dependent Nrf2 activation. Besides MAPK, protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), and RNA-dependant protein kinase-like endoplasmic reticulum kinase (PERK), depending on cell types and agent properties, have been also implicated in Nrf2 activation. Other transcription factors that also regulate HO-1 expression include heat-shock factor (HSF), nuclear factor-erythroid 2 (NF-E2), activator protein-1 (AP-1), and nuclear factor-κB (NF-κB). Upon external stimuli, the active forms of these transcription factors translocate to the nucleus where they bind to the specific DNA sequence leading to the transcription of HO-1 gene. Some phytochemicals directly activate Nrf2 nuclear translocation or indirectly through ROS generation.
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Figure 1: Signaling pathways leading to HO-1 expression by phytochemicals and drugs through MAPK-dependent Nrf2 activation. Besides MAPK, protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), and RNA-dependant protein kinase-like endoplasmic reticulum kinase (PERK), depending on cell types and agent properties, have been also implicated in Nrf2 activation. Other transcription factors that also regulate HO-1 expression include heat-shock factor (HSF), nuclear factor-erythroid 2 (NF-E2), activator protein-1 (AP-1), and nuclear factor-κB (NF-κB). Upon external stimuli, the active forms of these transcription factors translocate to the nucleus where they bind to the specific DNA sequence leading to the transcription of HO-1 gene. Some phytochemicals directly activate Nrf2 nuclear translocation or indirectly through ROS generation.

Mentions: A number of intracellular signaling molecules and their downstream transcription factors have been identified to involve HO-1 expression [13]. Among them, the mitogen-activated protein kinase (MAPK), as one of upstream pathways, and the nuclear factor E2-related factor 2 (Nrf2), as one of downstream transcription factors, are well described to be more important in HO-1 expression by non-toxic phytochemicals and drugs [13, 14], and thus briefly discussed below (Fig. 1).


Integrative survival response evoked by heme oxygenase-1 and heme metabolites.

Pae HO, Kim EC, Chung HT - J Clin Biochem Nutr (2008)

Signaling pathways leading to HO-1 expression by phytochemicals and drugs through MAPK-dependent Nrf2 activation. Besides MAPK, protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), and RNA-dependant protein kinase-like endoplasmic reticulum kinase (PERK), depending on cell types and agent properties, have been also implicated in Nrf2 activation. Other transcription factors that also regulate HO-1 expression include heat-shock factor (HSF), nuclear factor-erythroid 2 (NF-E2), activator protein-1 (AP-1), and nuclear factor-κB (NF-κB). Upon external stimuli, the active forms of these transcription factors translocate to the nucleus where they bind to the specific DNA sequence leading to the transcription of HO-1 gene. Some phytochemicals directly activate Nrf2 nuclear translocation or indirectly through ROS generation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2386522&req=5

Figure 1: Signaling pathways leading to HO-1 expression by phytochemicals and drugs through MAPK-dependent Nrf2 activation. Besides MAPK, protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), and RNA-dependant protein kinase-like endoplasmic reticulum kinase (PERK), depending on cell types and agent properties, have been also implicated in Nrf2 activation. Other transcription factors that also regulate HO-1 expression include heat-shock factor (HSF), nuclear factor-erythroid 2 (NF-E2), activator protein-1 (AP-1), and nuclear factor-κB (NF-κB). Upon external stimuli, the active forms of these transcription factors translocate to the nucleus where they bind to the specific DNA sequence leading to the transcription of HO-1 gene. Some phytochemicals directly activate Nrf2 nuclear translocation or indirectly through ROS generation.
Mentions: A number of intracellular signaling molecules and their downstream transcription factors have been identified to involve HO-1 expression [13]. Among them, the mitogen-activated protein kinase (MAPK), as one of upstream pathways, and the nuclear factor E2-related factor 2 (Nrf2), as one of downstream transcription factors, are well described to be more important in HO-1 expression by non-toxic phytochemicals and drugs [13, 14], and thus briefly discussed below (Fig. 1).

Bottom Line: The mechanism of protective actions of HO-1 has not been completely elucidated, but recent evidence suggests that one or more of heme metabolites can mediate the protective effects of HO-1.Many of these effects of CO depend on the production of cyclic guanosine monophosphate (cGMP), and the modulation of mitogen-activated protein kinase (MAPK) pathways.In addition, the cytoprotective roles of HO-1 shall be discussed from the perspective of each of the metabolic by-products.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.

ABSTRACT
Heme oxygenase (HO) catalyzes the rate-limiting step in heme degradation to produce carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently converted to bilirubin by its reductase, and iron is recycled for heme synthesis. The inducible HO isoform, HO-1, is involved in the protection of multiple tissues and organs. The mechanism of protective actions of HO-1 has not been completely elucidated, but recent evidence suggests that one or more of heme metabolites can mediate the protective effects of HO-1. Particularly, CO mimics the antioxidant, anti-inflammatory, anti-apoptotic and antiproliferative actions of HO-1. Many of these effects of CO depend on the production of cyclic guanosine monophosphate (cGMP), and the modulation of mitogen-activated protein kinase (MAPK) pathways. The transcription factors, including nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases, including MAPK pathway, play an important regulatory role in HO-1 expression by dietary antioxidants and drugs. This review attempts to concisely summarize the molecular and biochemical characteristics of HO-1, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by dietary antioxidants and drugs. In addition, the cytoprotective roles of HO-1 shall be discussed from the perspective of each of the metabolic by-products.

No MeSH data available.