ArticleToxicology and industrial health
Signaling pathways involved in phase II gene induction by alpha, beta-unsaturated aldehydes.
Article in Toxicology and industrial health. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 64 citations in OpenAlex.
- Resibufogenin ameliorates cerebral ischemia-reperfusion injury by modulating microglial redox homeostasis via Keap1-Nrf2-TFR1/ARE axis.Acta pharmacologica Sinica · 2026Article
- ALDH2 Mediated Ferroptosis Regulation in Ischemia-Reperfusion Injury.Journal of cellular and molecular medicine · 2026Review
- Mechanisms and preventive measures of ALDH2 in ischemia‑reperfusion injury: Ferroptosis as a novel target (Review).Molecular medicine reports · 2025Review
- Role of Oxidative Stress and Nrf2/KEAP1 Signaling in Colorectal Cancer: Mechanisms and Therapeutic Perspectives with Phytochemicals.Antioxidants (Basel, Switzerland) · 2021Review
- Age-Related Neuronal Deterioration Specifically Within the Dorsal CA1 Region of the Hippocampus in a Mouse Model of Late Onset Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2021Article
- The Cutaneous Physiological Redox: Essential to Maintain but Difficult to Define.Antioxidants (Basel, Switzerland) · 2020Article
- Cholestatic liver disease results increased production of reactive aldehydes and an atypical periportal hepatic antioxidant response.Free radical biology & medicine · 2019Article
- Zerumbone Exhibits Antiphotoaging and Dermatoprotective Properties in Ultraviolet A-Irradiated Human Skin Fibroblast Cells via the Activation of Nrf2/ARE Defensive Pathway.Oxidative medicine and cellular longevity · 2019Article
- Review
- Nitro-fatty acids: New drug candidates for chronic inflammatory and fibrotic diseases.Nitric oxide : biology and chemistry · 2018Review
- MiR-21-Mediated Suppression of Smad7 Induces TGFβ1 and Can Be Inhibited by Activation of Nrf2 in Alcohol-Treated Lung Fibroblasts.Alcoholism, clinical and experimental research · 2017Article
- 4-hydroxynonenal-mediated signaling and aging.Free radical biology & medicine · 2017Review
- Redox homeostasis: The Golden Mean of healthy living.Redox biology · 2016Article
- Oxidative stress response and Nrf2 signaling in aging.Free radical biology & medicine · 2015Review
- Integrated Haematological Profiles of Redox Status, Lipid, and Inflammatory Protein Biomarkers in Benign Obesity and Unhealthy Obesity with Metabolic Syndrome.Oxidative medicine and cellular longevity · 2015Article
- Modulation of keratinocyte expression of antioxidants by 4-hydroxynonenal, a lipid peroxidation end product.Toxicology and applied pharmacology · 2014Article
- Impact of cigarette smoke on the human and mouse lungs: a gene-expression comparison study.PloS one · 2014Article
- Cell death and diseases related to oxidative stress: 4-hydroxynonenal (HNE) in the balance.Cell death and differentiation · 2013Review
- Protein alkylation by the α,β-unsaturated aldehyde acrolein. A reversible mechanism of electrophile signaling?FEBS letters · 2013Article
- The generation of 4-hydroxynonenal, an electrophilic lipid peroxidation end product, in rabbit cornea organ cultures treated with UVB light and nitrogen mustard.Toxicology and applied pharmacology · 2013Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Phase II enzymes are induced primarily through the common electrophile response element (EpRE) signaling. Studies performed in different cell types and with different inducer appear to indicate variation in the upstream signaling pathways involved in the induction of these phase II genes. Nonetheless, whether variation in signaling among phase II genes in the same cell with the same inducer is unclear. This study is designed to answer this question using human bronchial epithelial cells (HBE1 cells) as a model and screening with a variety of protein kinase inhibitors with varying degrees of specificity. Two electrophiles, 4-hydroxynonenal (HNE) and acrolein, induced the expression of phase II genes (GCLC, GCLM, NQO1, NQO2, HO-1, and GSTM-1). Nrf2 silencing significantly decreased the induction of all of these genes, confirming the involvement of Nrf2-EpRE signaling. ERK and p38MAPK inhibitors had no effect, while a JNK inhibitor abrogated the GCLC and GCLM induction by HNE, but not that by acrolein. Among the PKC inhibitors used, one eliminated gene induction by HNE and acrolein, while two others showed no effects. One PI3K inhibitor decreased the induction of GCLM, NQO1, NQO2 and HO-1, but not GCLC and GST-M1; on the other hand, the inhibitory effects of another PI3K inhibitor on gene induction seems to be gene- and inducer- specific. In conclusion, our data suggest that although phase II genes are coordinately induced through Nrf2-EpRE signaling by electrophiles, the upstream signaling pathways involved are gene- and inducer- specific. It is also suggested that commercial kinase inhibitors may produce non-specific effects on phase II gene expression via mechanisms unrelated to their purported specificity.
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