Aryl Hydrocarbon Receptor Nuclear Translocator and Upstream Stimulatory Factor Regulate Cytochrome P450 2a5 Transcription through a Common E-box Site

Arpiainen, Satu; Lämsä, Virpi; Pelkonen, Olavi; Yim, Sun Hee; Gonzalez, Frank J.; Hakkola, Jukka

doi:10.1016/j.jmb.2007.03.075

Cited by 20 publications

(25 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Later, Arpiainen et al (2007) further demonstrated that ARNT can homodimerize and bind to the E-box which is located at position -2403 to -2398 in the Cyp2a5 promoter .…”

Section: Arpiainen Et Al (2005) Identified a Putative Ahr Response Ementioning

confidence: 98%

“…Arpiainen et al (2007) showed that USF-1 and USF-2a also bind to the E-box, but requires HNF-4α to activate Cyp2a5 promoter, while ARNT transactivation was independent of HNF-4α .…”

Section: Arpiainen Et Al (2005) Identified a Putative Ahr Response Ementioning

confidence: 99%

“…To date, a number of transcription factors and their response elements have been identified for CYP2A5 that play important roles in various cellular functions such as the stress and immune responses, cell cycle activation and cellular proliferation, and glucose and xenobiotic metabolism (Cai et al, 2002;Maglich et al, 2002;Abu-Bakar et al, 2004;Ulvila et al, 2004;Abu-bakar et al, 2007;Arpiainen et al, 2007Arpiainen et al, , 2008. However, given that effects of high BR has been shown to be closely related to oxidative stress in various organelles, among the other transcription factors, Nrf2 appears to be involved in BR-mediated induction of CYP2A5.…”

Section: Cyp2a5 Overexpressing Microsomes Have Increased Br Degradatimentioning

confidence: 99%

“…Since then, a number of transcription factors for Cyp2a5 and their response elements in the Cyp2a5 promoter region have been identified. The transcription factors identified to date, such as aryl hydrocarbon receptor (AhR), aryl hydrocarbon receptor nuclear translocator (ARNT), upstream stimulatory factors (USF-1 and USF-2), hepatic nuclear facor-4-alpha (HNF-4α), nuclear factor I (NF-I), constitutive androstane receptor (CAR), and nuclear factor-E2 p45-related factor 2 (Nrf2) have been shown to play an important role in cellular stress and the immune response, oxidative stress and detoxification of xenobiotics, cell cycle and proliferation, and lipid and glucose metabolism (Cai et al, 2002;Maglich et al, 2002;Abu-Bakar et al, 2004;Ulvila et al, 2004;Abu-bakar et al, 2007;Arpiainen et al, 2007Arpiainen et al, , 2008Kirby et al, 2011).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

Kim

Antenos

Squires

et al. 2013

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Murine cytochrome P450 2A5 (CYP2A5) is an interesting enzyme for its unique regulation and its involvement in liver injury caused by various well-known pathological conditions or hepatotoxins. It has been reported that CYP2A5 is upregulated following exposure to chemical hepatotoxins and during pathophysiological conditions in which the levels of most Cytochrome P450s are either unchanged or down-regulated. Recently bilirubin has been identified as the first endogenous substrate for CYP2A5 and it has been suggested that CYP2A5 plays a major role in bilirubin clearance as an alternative mechanism to BR conjugation by UGT1A1. This study investigated the mechanisms of gene regulation and cytoprotective role of CYP2A5 in response to bilirubin treatment in liver. Our results demonstrate that bilirubin induces CYP2A5 expression at the mRNA and protein levels by increasing CYP2A5 transcription via a mechanism that involves Nrf2 activation. Furthermore, our results suggest that induced CYP2A5 plays a cytoprotective role against bilirubin toxicity by directly lowering the cellular levels of bilirubin and by inhibiting caspase-3 activation.iii ACKNOWLEDGEMENTS

show abstract

“…Later, Arpiainen et al (2007) further demonstrated that ARNT can homodimerize and bind to the E-box which is located at position -2403 to -2398 in the Cyp2a5 promoter .…”

Section: Arpiainen Et Al (2005) Identified a Putative Ahr Response Ementioning

confidence: 98%

“…Arpiainen et al (2007) showed that USF-1 and USF-2a also bind to the E-box, but requires HNF-4α to activate Cyp2a5 promoter, while ARNT transactivation was independent of HNF-4α .…”

Section: Arpiainen Et Al (2005) Identified a Putative Ahr Response Ementioning

confidence: 99%

Section: Cyp2a5 Overexpressing Microsomes Have Increased Br Degradatimentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

Kim

Antenos

Squires

et al. 2013

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

show abstract

“…In addition, under a hypoxia condition, ARNT dimerizes with HIF1α to upregulate the expression of genes involved in angiogenesis and tumorigenesis (Ke and Costa, 2006). Furthermore, ARNT homodimer binds to palindromic enhancer box (E-box) sequence to upregulate the expression of some genes such as mouse Cyp2a5 (Arpiainen et al, 2007). In the human genome, more than 13,000 putative ARNT binding sites have been estimated to exist by in silico analysis (Gunton et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Aryl hydrocarbon receptor nuclear translocator in human liver is regulated by miR-24

Oda

Nakajima

Mohri

et al. 2012

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Aryl hydrocarbon receptor nuclear translocator (ARNT) forms a heterodimer with aryl hydrocarbon receptor or hypoxia inducible factor 1α to mediate biological responses to xenobiotic exposure and hypoxia. Although the regulation mechanism of the ARNT expression is largely unknown, earlier studies reported that the human ARNT protein level was decreased by hydrogen peroxide or reactive oxygen species. These stimuli increase the miR-24 level in various human cell lines. In silico analysis predicts that some microRNAs miR-24 would be one of the factors underlying the mechanisms by which ARNT protein is decreased by reactive oxygen species.

show abstract

ARNT: A Key bHLH/PAS Regulatory Protein Across Multiple Pathways

Dougherty

Pollenz

2010

Comprehensive Toxicology

View full text Add to dashboard Cite

Aryl Hydrocarbon Receptor Nuclear Translocator and Upstream Stimulatory Factor Regulate Cytochrome P450 2a5 Transcription through a Common E-box Site

Cited by 20 publications

References 66 publications

Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

Aryl hydrocarbon receptor nuclear translocator in human liver is regulated by miR-24

ARNT: A Key bHLH/PAS Regulatory Protein Across Multiple Pathways

Contact Info

Product

Resources

About