The sigma-1 receptor protects against cellular oxidative stress and activates antioxidant response elements.
Open accessAbstract
Sigma-1 receptors are associated with Alzheimer's disease, major depressive disorders, and schizophrenia. These receptors show progrowth/antiapoptotic properties via their chaperoning functions to counteract ER (endoplasmic reticulum) stress, to block neurodegeneration, and to regulate neuritogenesis. The sigma-1 receptor knock out mouse offered an opportunity to assess possible mechanisms by which the sigma-1 receptor modulates cellular oxidative stress. Nuclear magnetic resonance (NMR) metabolomic screening of the WT (wild type) and sigma-1 KO (knockout) livers was performed to investigate major changes in metabolites that are linked to oxidative stress. Significant changes in protein levels were also identified by two-dimensional (2D) gel electrophoresis and mass spectrometry. Increased levels of the antioxidant protein peroxiredoxin 6 (Prdx6), and the ER chaperone BiP (GRP78) compared to WT littermates were detected. Oxidative stress was measured in WT and sigma-1 KO mouse liver homogenates, in primary hepatocytes and in lung homogenates. Furthermore, sigma-1 receptor mediated activation of the antioxidant response element (ARE) to upregulate NAD(P)H quinone oxidoreductase 1 (NQO1) and superoxide dismutase 1 (SOD1) mRNA expression in COS cells was shown by RT PCR. These novel functions of the sigma-1 receptor were sensitive to well-known sigma ligands via their antagonist/agonist properties.
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Sig-1R protects cells against reactive oxygen species and activates antioxidant response elements.
“Sig-1R also protects the cells against reactive oxygen species and activates the antioxidant response elements (Pal et al., 2012), therefore Sig-1R agonists such as DMT may function as indirect antioxidants.”
From The therapeutic potentials of Ayahuasca: possible effects against various diseases of civilization (2016) · cites this paper as Pal et al., 2012
Sig-1R agonists such as DMT may function as indirect antioxidants.
“Sig-1R also protects the cells against reactive oxygen species and activates the antioxidant response elements (Pal et al., 2012), therefore Sig-1R agonists such as DMT may function as indirect antioxidants.”
From The therapeutic potentials of Ayahuasca: possible effects against various diseases of civilization (2016) · cites this paper as Pal et al., 2012
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- Authors
- Pal, A., Fontanilla, D., Gopalakrishnan, A., Chae, Y.-K., Markley, J. L., & Ruoho, A. E.
- Affiliations
- University of Wisconsin–Madison (US)
- Sejong University (KR)
- Corresponding author
- Ruoho, Arnold E.
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 682
- Issue
- 1-3
- Pages
- 12-20
- ISSN
- 0014-2999 (ISSN-L)
- PMC
- PMC3314091
- OpenAlex
- W2093330856
- Cited by
- 177
- References
- 61
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 15 · 2023: 7 · 2022: 14 · 2021: 17 · 2020: 12 · 2019: 16 · 2018: 7 · 2017: 15 · 2016: 16 · 2015: 13 · 2014: 13 · 2013: 10 · 2012: 2
- FWCI
- 5.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (MH065503)
- Retina Research Foundation Edwin and Dorothy Gamewell Professorship
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- sigma-1 receptor, oxidative stress, antioxidant response element, NQO1, superoxide dismutase 1, peroxiredoxin 6, BiP/GRP78, endoplasmic reticulum stress, sigma receptor ligands, hepatocytes, liver metabolomics, neuroprotection
- MeSH terms
- Endoplasmic Reticulum Chaperone BiP, Sigma-1 Receptor, Animals, Antioxidants, Chlorocebus aethiops, Guinea Pigs, Receptors, sigma, Oxidative Stress, COS Cells, Response Elements, Proteomics, Mice, Gene Knockout Techniques
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