ArticleMolecular neurobiology2016
Nuclear Factor-kappaB-Dependent Sestrin2 Induction Mediates the Antioxidant Effects of BDNF Against Mitochondrial Inhibition in Rat Cortical Neurons.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 64 citations in OpenAlex.
- Propolis alleviates brain tissue damage and oxidative abnormalities in streptozotocin (STZ)-induced diabetes.Journal, genetic engineering & biotechnology · 2026Article
- Reactive oxygen species and antioxidant strategies in human sperm cryodamage.Frontiers in medicine · 2026Review
- Secretome from Uterine Cervical Mesenchymal Stem Cells as a Protector of Neuronal Cells Against Oxidative Stress and Inflammation.Biomolecules · 2025Article
- Serum BDNF and progression to MCI in cognitively normal older adults: A prospective cohort study.The journal of prevention of Alzheimer's disease · 2025Article
- BDNF-TrkB Signaling in Mitochondria: Implications for Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Stem cells alleviate OGD/R mediated stress response in PC12 cells following a co-culture: modulation of the apoptotic cascade through BDNF-TrkB signaling.Cell stress & chaperones · 2023Article
- Article
- Sestrin2: multifaceted functions, molecular basis, and its implications in liver diseases.Cell death & disease · 2023Review
- Sestrin2 in diabetes and diabetic complications.Frontiers in endocrinology · 2023Review
- The Function of BDNF and Its Receptor in the Male Genitourinary System and Its Potential Clinical Application.Current issues in molecular biology · 2022Review
- Association of plasma brain-derived neurotrophic factor levels and frailty in community-dwelling older adults.Scientific reports · 2022Article
- The role of growth factors in human sperm parameters: A review of in vitro studies.International journal of reproductive biomedicine · 2022Review
- Histopathologic evaluation of the inflammatory factors and stromal cells in the endometriosis lesions: A case-control study.International journal of reproductive biomedicine · 2022Article
- Regulation of Oxidative Stress by Long Non-coding RNAs in Central Nervous System Disorders.Frontiers in molecular neuroscience · 2022Review
- Sestrin2 in hypoxia and hypoxia-related diseases.Redox report : communications in free radical research · 2021Review
- Potential Roles of Sestrin2 in Alzheimer's Disease: Antioxidation, Autophagy Promotion, and Beyond.Biomedicines · 2021Review
- Exploring Hyperoxia Effects in Cancer-From Perioperative Clinical Data to Potential Molecular Mechanisms.Biomedicines · 2021Review
- Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle-Do Myokines Play a Role?Antioxidants (Basel, Switzerland) · 2021Review
- Target Sestrin2 to Rescue the Damaged Organ: Mechanistic Insight into Its Function.Oxidative medicine and cellular longevity · 2021Review
- Reduction in Nesfatin-1 Levels in the Cerebrospinal Fluid and Increased Nigrostriatal Degeneration Following Ventricular Administration of Anti-nesfatin-1 Antibody in Mice.Frontiers in neuroscience · 2021Article
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain-derived neurotrophic factor (BDNF), in addition to its neurotrophic action, also possesses antioxidant activities. However, the underlying mechanisms remain to be fully defined. Sestrin2 is a stress-responsive gene implicated in the cellular defense against oxidative stress. Currently, the potential functions of sestrin2 in nervous system, in particular its correlation with neurotrophic factors, have not been well established. In this study, we hypothesized that BDNF may enhance sestrin2 expression to confer neuronal resistance against oxidative stress induced by 3-nitropropionic acid (3-NP), an irreversible mitochondrial complex II inhibitor, and characterized the molecular mechanisms underlying BDNF induction of sestrin2 in primary rat cortical cultures. We found that BDNF-mediated sestrin2 expression in cortical neurons required formation of nitric oxide (NO) with subsequent production of 3',5'-cyclic guanosine monophosphate (cGMP) and activation of cGMP-dependent protein kinase (PKG). BDNF induced localization of nuclear factor-kappaB (NF-κB) subunits p65 and p50 into neuronal nuclei that required PKG activities. Interestingly, BDNF exposure led to formation of a protein complex containing at least PKG-1 and p65/p50, which bound to sestrin2 promoter with resultant upregulation of its protein products. Finally, BDNF preconditioning mitigated production of reactive oxygen species (ROS) as a result of 3-NP exposure; this antioxidative effect of BDNF was dependent upon PKG activity, NF-κB, and sestrin2. Taken together, our results indicated that BDNF enhances sestrin2 expression to confer neuronal resistance against oxidative stress induced by 3-NP through attenuation of ROS formation; furthermore, BDNF induction of sestrin2 requires activation of a pathway involving NO/PKG/NF-κB.
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