Anthocyanins Induce the Activation of Phase II Enzymes through the Antioxidant Response Element Pathway against Oxidative Stress-Induced Apoptosis

In developing animals, Cadmium (Cd) induces toxicity to many organs including brain. Reactive oxygen species (ROS) are often implicated in Cd-inducedtoxicity and it has been clearly demonstrated that oxidative stress interferes with the expression of genes as well as transcriptional factors such as Nrf2-dependent Antioxidant Response Element (Nrf2-ARE). Cd-generated oxidative stress and elevated Nrf2 activity have been reportedin vitroandin situcells. In this study we evaluated the morphological changes and the expression pattern of Nrf2 and correlated them with the Cd concentrations in different ages of developing rats in heart, lung, kidney, liver, and brain. The Cd content in different organs of rats treated with the metal was increased in all ages assayed. Comparatively, lower Cd brain levels were found in rats intoxicated at the age of 12 days, then pups treated at 5, 10, or 15 days old, at the same metal dose. No evident changes, as a consequence of cadmium exposure, were evident in the morphological analysis in any of the ages assayed. However, Nrf2-ARE immunoreactivity was observed in 15-day-old rats exposed to Cd. Our results support that fully developed blood-brain barrier is an important protector against Cd entrance to brain and that Nrf2 increased expression is a part of protective mechanism against cadmium-induced toxicity.

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Astragaloside IV Protects Against Oxidative Stress in Calf Small Intestine Epithelial Cells via NFE2L2-Antioxidant Response Element Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms20246131 ◽

2019 ◽

Vol 20 (24) ◽

pp. 6131 ◽

Cited By ~ 2

Author(s):

Yafang Wang ◽

Fugui Jiang ◽

Haijian Cheng ◽

Xiuwen Tan ◽

Yifan Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Small Intestine ◽

Epithelial Cells ◽

Reactive Oxygen Species Generation ◽

Antioxidant Response ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Antioxidant Response Element ◽

Astragaloside Iv ◽

Response Element

Oxidative stress can damage intestinal epithelial cell integrity and function, causing gastrointestinal disorders. Astragaloside IV (ASIV) exhibits a variety of biological and pharmacological properties, including anti-inflammatory and antioxidant effects. The purpose of this research was to investigate the cytoprotective action of ASIV and its mechanisms in calf small intestine epithelial cells with hydrogen peroxide (H2O2)-induced oxidative stress. ASIV pretreatment not only increased cell survival, but it also decreased reactive oxygen species generation and apoptosis, enhanced superoxide dismutase, catalase, and glutathione peroxidase levels, and it reduced malondialdehyde formation. Furthermore, pretreatment with ASIV elevated the mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (NFE2L2), heme oxygenase-1 (HMOX1), and NAD(P)H quinone dehydrogenase 1 (NQO1). The NFE2L2 inhibitor ML385 inhibited NFE2L2 expression and then blocked HMOX1 and NQO1 expression. These results demonstrate that ASIV treatment effectively protects against H2O2-induced oxidative damage in calf small intestine epithelial cells through the activation of the NFE2L2-antioxidant response element signaling pathway.

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Apoptosis Signal-Regulating Kinase-1 (ASK-1) Knockdown Augments Antioxidant Response Element (ARE)-Mediated Gene Expression Of Phase-II Antioxidant Enzymes (AOES) During Acute Hyperoxia (HO) Exposure

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a5971 ◽

2011 ◽

Author(s):

Patrudu S. Makena ◽

Manik C. Ghosh ◽

Vijay K. Gorantla ◽

Lavanya Bezawada ◽

Charlean L. Luellen ◽

...

Keyword(s):

Gene Expression ◽

Antioxidant Enzymes ◽

Phase Ii ◽

Antioxidant Response ◽

Antioxidant Response Element ◽

Response Element

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Conditioned Media of Choroid Plexus Epithelial Cells Induces Nrf2-Activated Phase II Antioxidant Response Proteins and Suppresses Oxidative Stress-Induced Apoptosis in PC12 Cells

Journal of Molecular Neuroscience ◽

10.1007/s12031-014-0228-4 ◽

2014 ◽

Vol 53 (4) ◽

pp. 617-625 ◽

Cited By ~ 6

Author(s):

Abbas Aliaghaei ◽

Fariba Khodagholi ◽

Abolhassan Ahmadiani

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Choroid Plexus ◽

Pc12 Cells ◽

Phase Ii ◽

Antioxidant Response ◽

Conditioned Media ◽

Induced Apoptosis ◽

Choroid Plexus Epithelial

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Nitric Oxide-induced Transcriptional Up-regulation of Protective Genes by Nrf2 via the Antioxidant Response Element Counteracts Apoptosis of Neuroblastoma Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m312492200 ◽

2004 ◽

Vol 279 (19) ◽

pp. 20096-20107 ◽

Cited By ~ 114

Author(s):

Saravanakumar Dhakshinamoorthy ◽

Alan G. Porter

Keyword(s):

Nitric Oxide ◽

Neuroblastoma Cells ◽

Antioxidant Response ◽

Gene Induction ◽

Nuclear Accumulation ◽

Antioxidant Response Element ◽

Response Element ◽

Protective Genes ◽

Detoxifying Enzyme ◽

Induced Apoptosis

Nitric oxide (NO) is a signaling molecule that in excess causes cell death. Here we report a mechanism of NO-induced transcriptional up-regulation of genes encoding detoxifying enzymes and protective proteins and their role in counteracting NO-induced apoptosis of neuroblastoma cells. Promoter analysis using reporter assays identified the antioxidant response element (ARE) located in the promoter region of NAD(P)H:quinone oxidoreductase 1 (Nqo1) and other detoxifying enzyme genes as responsible for NO-mediated gene induction. The transcription factors NF-E2-related factor 2 (Nrf2) and small maf proteins were detected in NO-induced nuclear protein-ARE complexes. Nrf2 augmented NO-induced, ARE-dependent gene expression, which was blocked by dominant-negative Nrf2 (DN-Nrf2) lacking the transcriptional activation domain. Consistent with these results, Nrf2 was localized in the cytoplasm in unstimulated cells, and NO triggered its rapid nuclear accumulation. Neuroblastoma cells were stably transfected with DN-Nrf2, which repressed both the expression of protective genes and their induction by NO. These DN-Nrf2 cells exhibited reduced NQO1 enzymatic activity and were sensitized to NO-induced apoptosis. Similar results were obtained when Nrf2 expression was blocked by RNA interference. Conversely, stable cells expressing higher levels of Nrf2 protein had elevated NQO1 activity and were protected from NO. Finally, NO-mediated ARE-dependent gene induction occurred well before apoptosis as judged by caspase activation. These results together suggest that NO signals the transcriptional up-regulation of NQO1 and other detoxifying enzyme and protective genes through Nrf2 via the ARE to counteract NO-induced apoptosis of neuroblastoma cells.

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