Involvement of the electrophile responsive element and p53 in the activation of hepatic stellate cells as a response to electrophile menadione

Vasiliou, Vasilis; Qamar, Lubna; Pappa, Aglaia; Sophos, Nickolas A.; Petersen, Dennis R.

doi:10.1016/s0003-9861(03)00095-x

Cited by 17 publications

(12 citation statements)

References 33 publications

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“…We found that the peroxide rose from 2.5 lM/mg protein in control cells to 24 lM 1 h after leptin treatment. Since the TD (toxicity dose) 50 for H 2 O 2 in rat HSCs and in a HSC line has been reported to be 280-310 lM [32], the level of H 2 O 2 (24 lM) generated in LX-2 cells by leptin is unlikely to elicit toxicity and cell death; rather the H 2 O 2 serves as a second messenger in ERK1/2 and p38 signal transduction. This interpretation is consistent with the observations that H 2 O 2 at a 25-50 lM concentration mediates signaling through p38 to up-regulate a1(I) collagen mRNA in response to TGF-b and acetaldehyde in HSCs [33][34][35].…”

Section: Discussionmentioning

confidence: 99%

Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells

Cao

Mak

Lieber

2007

Journal of Hepatology

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Section: Discussionmentioning

confidence: 99%

Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells

Cao

Mak

Lieber

2007

Journal of Hepatology

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“…In response to accumulating mediators of oxidative stress and lipid peroxidation, stellate cells become "activated" and begin to proliferate and increase production of collagen. These changes are accompanied by acquired resistance of activated stellate cells in culture to injury mediated by electrophiles, such as menadione (Vasiliou et al, 2003). Resistance of activated stellate cells to electrophile cytotoxicity was hypothesized to be due to direct detoxification of menadione and/or increased scavenging of ROS (Vasiliou et al, 2003).…”

Section: Cytochrome P450 2e1-associated Oxidative Stressmentioning

confidence: 99%

Emerging Role of Nrf2 in Protecting Against Hepatic and Gastrointestinal Disease

2007

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Transcription factor NF-E2-related factor 2 (Nrf2) belongs to the basic region-leucine zipper family and is activated in response to electrophiles and reactive oxygen species. Nrf2 coordinately regulates the constitutive and inducible transcription of a wide array of genes involved in drug metabolism, detoxification, and antioxidant defenses. During periods of oxidative stress, Nrf2 is released from sequestration in the cytoplasm and translocates to the nucleus. Nrf2 binds antioxidant response elements (AREs) in the regulatory regions of target genes and activates transcription. Genetically modified mice lacking Nrf2 serve as a useful tool for identifying new ARE-regulated genes and assessing the ability of Nrf2 to confer protection against a variety of pathologies in numerous organs including the liver, intestine, lung, skin, and nervous system. With regards to the liver and gastrointestinal tract, Nrf2 knockout mice are more susceptible to acetaminophen-induced hepatocellular injury, benzo[a]pyrene-induced tumor formation and Fasand TNFα-mediated hepatocellular apoptosis. The higher sensitivity of Nrf2 knockout mice to chemical toxicity is due in part to reduced basal and inducible expression of detoxification enzymes. Nrf2 may also be important in protecting against liver fibrosis, gallstone development, and formation of aberrant crypt foci. Research of Nrf2 has opened up new opportunities in understanding how antioxidant defense pathways are regulated, how oxidative stress contributes to disease progression and may serve as a novel target for designing therapies to prevent and treat diseases in which oxidative stress is implicated.

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“…The transcription factor Nrf2 mediates ARE/EpRE signaling, affects p53 stabilization (Vasiliou et al, 2003), and modulates expression of NF-B family members (Yang et al, 2005). Nrf2 protein levels increase in various systems when exposed to chemopreventive compounds (Chen and Kong, 2004).…”

Section: Cape Alters Alkylating Agent-induced Signalingmentioning

confidence: 99%

Bifunctional Alkylating Agent-Induced p53 and Nonclassical Nuclear Factor κB Responses and Cell Death Are Altered by Caffeic Acid Phenethyl Ester: A Potential Role for Antioxidant/Electrophilic Response-Element Signaling

Minsavage

Dillman²

2007

J Pharmacol Exp Ther

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Bifunctional alkylating agents (BFA) such as mechlorethamine (nitrogen mustard) and bis-(2-chloroethyl) sulfide (sulfur mustard; SM) covalently modify DNA and protein. The roles of nuclear factor B (NF-B) and p53, transcription factors involved in inflammatory and cell death signaling, were examined in normal human epidermal keratinocytes (NHEK) and immortalized HaCaT keratinocytes, a p53-mutated cell line, to delineate molecular mechanisms of action of BFA. NHEK and Ha-

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Involvement of the electrophile responsive element and p53 in the activation of hepatic stellate cells as a response to electrophile menadione

Cited by 17 publications

References 33 publications

Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells

Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic stellate cells

Emerging Role of Nrf2 in Protecting Against Hepatic and Gastrointestinal Disease

Bifunctional Alkylating Agent-Induced p53 and Nonclassical Nuclear Factor κB Responses and Cell Death Are Altered by Caffeic Acid Phenethyl Ester: A Potential Role for Antioxidant/Electrophilic Response-Element Signaling

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