ArticleBrain research2011
Hyperglycemia magnifies Schwann cell dysfunction and cell death triggered by PA-induced lipotoxicity.
Article in Brain research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 104 citations in OpenAlex.
- Diabetes and the Metabolic Syndrome as Drivers of Neurodegeneration: Convergent Mechanisms Linking Peripheral Neuropathy and Dementia.Annals of neurology · 2026Review
- Docosahexaenoic Acid Protects Schwann Cells Against Palmitic Acid-Induced Lipotoxicity by Modulating Autophagy, ER Stress, and Lipid Handling.Neurochemical research · 2026Article
- Innovative strategies for diabetic peripheral neuropathy: From clinical management to emerging bioengineering solutions.Bioactive materials · 2026Review
- Docosahexaenoic Acid Modulates Autophagy and Confers Neuronal Resilience under Hypoxia-Reoxygenation Stress.Journal of molecular neuroscience : MN · 2026Article
- Translating Basic Science to Clinical Applications: A Narrative Review of Repurposed Pharmacological Agents in Preclinical Models of Diabetic Neuropathy.Biomedicines · 2025Review
- Diabetic neuropathy: cutting-edge research and future directions.Signal transduction and targeted therapy · 2025Review
- Development and validation of a risk prediction model for painful diabetic peripheral neuropathy in type 2 diabetes mellitus: a multicenter retrospective study.Frontiers in endocrinology · 2025Article
- Article
- Unveiling the Role of Schwann Cell Plasticity in the Pathogenesis of Diabetic Peripheral Neuropathy.International journal of molecular sciences · 2024Review
- Establishment and external validation of an early warning model of diabetic peripheral neuropathy based on random forest and logistic regression.BMC endocrine disorders · 2024Article
- Correlation between thyroid hormone sensitivity and diabetic peripheral neuropathy in euthyroid patients with type 2 diabetes mellitus.Scientific reports · 2024Article
- Biomarkers and signaling pathways of diabetic nephropathy and peripheral neuropathy: possible therapeutic intervention of rutin and quercetin.Diabetology international · 2024Review
- How inflammation dictates diabetic peripheral neuropathy: An enlightening review.CNS neuroscience & therapeutics · 2024Review
- Article
- Immortalized Schwann cell lines as useful tools for pathogenesis-based therapeutic approaches to diabetic peripheral neuropathy.Frontiers in endocrinology · 2024Review
- Diabetic peripheral neuropathy based on Schwann cell injury: mechanisms of cell death regulation and therapeutic perspectives.Frontiers in endocrinology · 2024Review
- Effect of necrostatin-1 on sciatic nerve crush injury in rat models.Journal of orthopaedic surgery and research · 2023Article
- Melatonin ameliorates high glucose-induced autophagy in Schwann cells.International journal of biochemistry and molecular biology · 2023Article
- Diabetic neuropathy: Past, present, and future.Caspian journal of internal medicine · 2023Review
- Identification of Adipogenesis Subgroups and Immune Infiltration Characteristics in Diabetic Peripheral Neuropathy.Journal of immunology research · 2023Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Lipid overload resulting in lipotoxicity is prominent in a number of chronic diseases and has been associated with cellular dysfunction and cell death. This study characterizes palmitic acid-induced lipotoxicity (PA-LTx) in Schwann cell cultures grown in normal and high glucose concentrations. The study shows for the first time that Schwann cell (SC) cultures exposed to elevated levels of PA exhibit a dose- and time-dependent loss in cell viability. Hoescht and Annexin V/7AAD staining confirmed cell death through apoptosis and the lipotoxic effect was more dramatic in SC cultures grown under high glucose conditions. The first indication of cellular dysfunction in treated SC cultures was a decrease in Ca(++) levels in the endoplasmic reticulum (ER, [Ca(++)](ER)) observed five minutes following the initial challenge with PA. This decrease in [Ca(++) ](ER) was followed by a significant increase in the expression of ER stress signature genes CHOP, Xbp1 and GRP78. The early ER stress response induced by PA-LTx was followed by a strong mitochondrial membrane depolarization. Flow cytometry using 2', 7'-dichlorodihydrofluorescein diacetate (H(2)DCFDA) showed an increase in oxidative stress within three to six hours after PA treatment. Treatment of cultures undergoing PA-LTx with the calcium chelator BAPTA-AM and the anti-oxidant MCI-186 significantly reversed the lipotoxic effect by decreasing the generation of ROS and significantly increasing cell viability. We conclude that lipotoxicity in Schwann cells results in cellular dysfunction and cell death that involves a robust ER stress response, mitochondrial dysfunction and an augmented state of cellular oxidative stress (ASCOS).
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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 OpenQuestion graph.