ArticleJournal of molecular neuroscience : MN2017
The Anti-Aging Effect of Erythropoietin via the ERK/Nrf2-ARE Pathway in Aging Rats.
Article in Journal of molecular neuroscience : MN, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Aging-Related Changes in the Injury Response of the Peripheral Nervous System.Neuroscience bulletin · 2026Review
- Article
- Angiogenic responses are enhanced by recombinant human erythropoietin in a model of periventricular white matter damage of neonatal rats through EPOR-ERK1 signaling.Journal of neuropathology and experimental neurology · 2024Article
- Carbon dioxide and MAPK signalling: towards therapy for inflammation.Cell communication and signaling : CCS · 2023Review
- Whether Erythropoietin can be a Neuroprotective Agent against Premature Brain Injury: Cellular Mechanisms and Clinical Efficacy.Current neuropharmacology · 2022Review
- Pachymic Acid Ameliorates Pulmonary Hypertension by Regulating Nrf2-Keap1-ARE Pathway.Current medical science · 2022Article
- Second-generation non-hematopoietic erythropoietin-derived peptide for neuroprotection.Redox biology · 2022Article
- The Role of PI3K/AKT and MAPK Signaling Pathways in Erythropoietin Signalization.International journal of molecular sciences · 2021Review
- Possibility of inducing tumor cell senescence during therapy.Oncology letters · 2021Review
- Re-Evaluating the Oxidative Phenotype: Can Endurance Exercise Save the Western World?Antioxidants (Basel, Switzerland) · 2021Review
- Dihydromyricetin promotes longevity and activates the transcription factors FOXO and AOP inAging · 2020Article
- Leonurine ameliorates D-galactose-induced aging in mice through activation of the Nrf2 signalling pathway.Aging · 2019Article
- Intranasal erythropoietin ameliorates neurological function impairments and neural pathology in mice with chronic alcoholism by regulating autophagy‑related Nrf2 degradation.Molecular medicine reports · 2019Article
- Regulation of Mitochondrial Biogenesis as a Way for Active Longevity: Interaction Between the Nrf2 and PGC-1α Signaling Pathways.Frontiers in genetics · 2019Review
- Anti-neovascularization effects of DMBT in age-related macular degeneration by inhibition of VEGF secretion through ROS-dependent signaling pathway.Molecular and cellular biochemistry · 2018Article
- Inosine improves cognitive function and decreases aging-induced oxidative stress and neuroinflammation in aged female rats.Inflammopharmacology · 2018Article
- Exercise Training Protects Against Aging-Induced Cognitive Dysfunction via Activation of the Hippocampal PGC-1α/FNDC5/BDNF Pathway.Neuromolecular medicine · 2018Article
- Erythropoietin suppresses D-galactose-induced aging of rats via the PI3K/Akt/Nrf2-ARE pathway.International journal of clinical and experimental pathology · 2018Article
- Memory enhancement and protective effects of crocin against D-galactose aging model in the hippocampus of Wistar rats.Iranian journal of basic medical sciences · 2017Article
- Current Perspective in the Discovery of Anti-aging Agents from Natural Products.Natural products and bioprospecting · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Erythropoietin (EPO) has a neuroprotective effect and can resist aging, which most likely occur through EPO increasing the activity of antioxidant enzymes and scavenging free radicals. In this study, we verified the anti-aging function of EPO and discussed the mechanism occurring through the extracellular signal-regulated kinase (ERK)/NF-E2-related factor 2 (Nrf2)-ARE pathway. A rat model of aging was induced by the continuous subcutaneous injection of 5 % D-galactose for 6 weeks. At the beginning of the sixth week, physiological saline or EPO was administered twice per day through a lateral ventricle system for a total of 7 days. In one group, 2 μl PD98059 was administered 30 min before EPO. Learning and memory ability were analyzed with the Morris water maze system. HE staining was used to observe the morphological changes in the neurons in the hippocampus, and immunohistochemical staining as well as Western blots were carried out to detect the expression of ERK for each group of rats and the expression of phosphorylated-ERK (P-ERK), Nrf2, and superoxide dismutase (SOD). Real-Time PCR was carried out to detect the amount of Nrf2 mRNA and the KEAP1 mRNA expression. EPO can significantly improve learning and memory ability in aging rats and can provide protection against aging by improving the hippocampus morphology. Immunohistochemical staining and Western blots showed P-ERK, Nrf2, and Cu-Zn SOD decreases in aging rats compared to the normal group, while the expression for those proteins increased after EPO intervention. PD98059 inhibited the enhanced expression of P-ERK, Nrf2, and Cu-Zn SOD induced by EPO. Real-Time PCR results suggested that the trend of Nrf2mRNA expression was the same as that for the proteins, which confirmed that the enhancement occurred at the gene level. As such, EPO can significantly resist or delay aging and protect the brain by reducing oxidative stress. The most likely mechanism is that EPO can promote the ERK/Nrf2-ARE pathway in aging rats and that PD98059 can inhibit that process. These findings may facilitate further studies on the mechanism of aging and applications for the neuroprotective properties of EPO for clinical treatments.
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