ArticleJournal of neurochemistry2020
Docosahexaenoic acid protection against palmitic acid-induced lipotoxicity in NGF-differentiated PC12 cells involves enhancement of autophagy and inhibition of apoptosis and necroptosis.
Article in Journal of neurochemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 27 citations in OpenAlex.
- Lipophagy: A key regulator in oxidative stress and metabolic disorders.Genes & diseases · 2026Review
- The nuclear receptor ESRRA is a crucial regulator of acute kidney injury through inhibition of the lipophagy-ferroptosis axis.Autophagy · 2026Article
- Docosahexaenoic Acid Protects Schwann Cells Against Palmitic Acid-Induced Lipotoxicity by Modulating Autophagy, ER Stress, and Lipid Handling.Neurochemical research · 2026Article
- Palmitic acid-induced autolysosomal dysfunction and lipotoxicity in neuroinflammation and neurodegeneration.Neural regeneration research · 2026Article
- Lipophagy in disease: signaling control, organelle communication, and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Diverse Forms of Autophagy and Their Roles in Liver Disease and Aging: A Comprehensive Review.Proteomes · 2026Review
- Docosahexaenoic Acid Modulates Autophagy and Confers Neuronal Resilience under Hypoxia-Reoxygenation Stress.Journal of molecular neuroscience : MN · 2026Article
- Lipid metabolism orchestrates liver regeneration: an integrated metabolic network.Journal of translational medicine · 2025Review
- TRAF6 integrates innate immune signals to regulate glucose homeostasis via Parkin-dependent and Parkin-independent mitophagy.Science advances · 2025Article
- The Impact of Polyunsaturated Fatty Acids in Cancer and Therapeutic Strategies.Current nutrition reports · 2025Review
- The protumorigenic enzyme GPAT2 inhibits arachidonic acid-triggered apoptosis in breast cancer.Lipids in health and disease · 2024Article
- Article
- The Interplay Between Autophagy and Regulated Necrosis.Antioxidants & redox signaling · 2023Review
- Omega-3 polyunsaturated fatty acids alleviate early brain injury after traumatic brain injury by inhibiting neuroinflammation and necroptosis.Translational neuroscience · 2023Article
- Fatty Acid-Binding Protein 4 Inhibition Promotes Locomotor and Autonomic Recovery in Rats following Spinal Cord Injury.Journal of neurotrauma · 2022Article
- Roles of the Unsaturated Fatty Acid Docosahexaenoic Acid in the Central Nervous System: Molecular and Cellular Insights.International journal of molecular sciences · 2022Review
- Fatty Acids: An Insight into the Pathogenesis of Neurodegenerative Diseases and Therapeutic Potential.International journal of molecular sciences · 2022Review
- The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders.Cell death & disease · 2022Review
- Longitudinal electrophysiological changes after mesenchymal stem cell transplantation in a spinal cord injury rat model.PloS one · 2022Article
- Transplantation of rat cranial bone-derived mesenchymal stem cells promotes functional recovery in rats with spinal cord injury.Scientific reports · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Lipotoxicity (LTx) leads to cellular dysfunction and cell death and has been proposed to be an underlying process during traumatic and hypoxic injuries and neurodegenerative conditions in the nervous system. This study examines cellular mechanisms responsible for docosahexaenoic acid (DHA 22:6 n-3) protection in nerve growth factor-differentiated pheochromocytoma (NGFDPC12) cells from palmitic acid (PAM)-mediated lipotoxicity (PAM-LTx). NGFDPC12 cells exposed to PAM show a significant lipotoxicity demonstrated by a robust loss of cell viability, apoptosis, and increased HIF-1α and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 gene expression. Treatment of NGFDPC12 cells undergoing PAM-LTx with the pan-caspase inhibitor ZVAD did not protect, but shifted the process from apoptosis to necroptosis. This shift in cell death mechanism was evident by the appearance of the signature necroptotic Topo I protein cleavage fragments, phosphorylation of mixed lineage kinase domain-like, and inhibition with necrostatin-1. Cultures exposed to PAM and co-treated with necrostatin-1 (necroptosis inhibitor) and rapamycin (autophagy promoter), showed a significant protection against PAM-LTx compared to necrostatin-1 alone. In addition, co-treatment with DHA, as well as 20:5 n-3, 20:4 n-6, and 22:5 n-3, in the presence of PAM protected NGFDPC12 cells against LTx. DHA-induced neuroprotection includes restoring normal levels of HIF-1α and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 transcripts and caspase 8 and caspase 3 activity, phosphorylation of beclin-1, de-phosphorylation of mixed lineage kinase domain-like, increase in LC3-II, and up-regulation of Atg7 and Atg12 genes, suggesting activation of autophagy and inhibition of necroptosis. Furthermore, DHA-induced protection was suppressed by the lysosomotropic agent chloroquine, an inhibitor of autophagy. We conclude that DHA elicits neuroprotection by regulating multiple cell death pathways including enhancement of autophagy and inhibiting apoptosis and necroptosis.
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