ArticleCell stress & chaperones2019
Melatonin ameliorates endoplasmic reticulum stress in N2a neuroblastoma cell hypoxia-reoxygenation injury by activating the AMPK-Pak2 pathway.
Article in Cell stress & chaperones, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Melatonin induces autophagy in neuroblastoma by alleviating Pak2‑mediated endoplasmic reticulum stress.Molecular medicine reports · 2026Article
- Parthenolide Exerts Protection against Hypoxic-Ischemic Brain Damage in Neonatal Rats by Inhibiting Perk-Mediated Endoplasmic Reticulum Stress.Molecular neurobiology · 2025Article
- CDC42 Regulates the ERK Pathway to Improve Oxygen‒Glucose Deprivation/Reoxygenation-Induced Neural Oxidative Stress and Apoptosis.Molecular neurobiology · 2025Article
- Targeting P21-Activated Kinase 2 as a Novel Therapeutic Approach to Mitigate Endoplasmic Reticulum Stress in Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2025Article
- Systematic review of melatonin in cerebral ischemia-reperfusion injury: critical role and therapeutic opportunities.Frontiers in pharmacology · 2024Review
- The Unfolded Protein Response: A Double-Edged Sword for Brain Health.Antioxidants (Basel, Switzerland) · 2023Review
- The Role of the Hypoxia-Related Unfolded Protein Response (UPR) in the Tumor Microenvironment.Cancers · 2022Review
- Human-rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic-ischemic pathway melatonin-sensitive.Journal of pineal research · 2022Article
- Insight of Melatonin: The Potential of Melatonin to Treat Bacteria-Induced Mastitis.Antioxidants (Basel, Switzerland) · 2022Review
- Melatonin and neuroblastoma: a novel therapeutic approach.Molecular biology reports · 2021Review
- VDAC Genes Expression and Regulation in Mammals.Frontiers in physiology · 2021Review
- Melatonin inhibits oxalate-induced endoplasmic reticulum stress and apoptosis in HK-2 cells by activating the AMPK pathway.Cell cycle (Georgetown, Tex.) · 2020Article
- Meteorin-Like (METRNL) Attenuates Myocardial Ischemia/Reperfusion Injury-Induced Cardiomyocytes Apoptosis by Alleviating Endoplasmic Reticulum Stress via Activation of AMPK-PAK2 Signaling in H9C2 Cells.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- SIRT1 Mediates Melatonin's Effects on Microglial Activation in Hypoxia: In Vitro and In Vivo Evidence.Biomolecules · 2020Article
- Unfolded protein response (UPR) integrated signaling networks determine cell fate during hypoxia.Cellular & molecular biology letters · 2020Review
- Melatonin Plays a Protective Role by Regulating miR-26a-5p-NRSF and JAK2-STAT3 Pathway to Improve Autophagy, Inflammation and Oxidative Stress of Cerebral Ischemia-Reperfusion Injury.Drug design, development and therapy · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress has been identified as a primary factor involved in brain ischemia-reperfusion injury progression. p21-activated kinase 2 (Pak2) is a novel ER function regulator. The aim of our study is to explore the influence of Pak2 on ER stress and determine whether melatonin attenuates ER stress-mediated cell death by modulating Pak2 expression in vitro using N2a cells. The results of our study demonstrated that hypoxia-reoxygenation (HR) injury repressed the levels of Pak2, an effect that was accompanied by activation of ER stress. In addition, decreased Pak2 was associated with oxidative stress, calcium overload, and caspase-12-mediated apoptosis activation in HR-treated N2a cells. Interestingly, melatonin treatment reversed the decreased Pak2 expression under HR stress. Knockdown of Pak2 abolished the protective effects of melatonin on ER stress, oxidative stress, and caspase-12-related N2a cells death. Additionally, we found that Pak2 was regulated by melatonin via the AMPK pathway; inhibition of AMPK prevented melatonin-mediated Pak2 upregulation, a result that was accompanied by an increase in N2a cell death. Altogether, these results identify the AMPK-Pak2 axis as a new signaling pathway responsible for ER stress and N2a cell viability under HR injury. Modulation of the AMPK-Pak2 cascade via supplementation of melatonin might be considered an effective approach to attenuate reperfusion-mediated N2a cell damage via repression of ER stress.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.