دورية أكاديمية
MitoTempo protects against nε-carboxymethyl lysine-induced mitochondrial dyshomeostasis and neuronal cells injury.
| العنوان: | MitoTempo protects against nε-carboxymethyl lysine-induced mitochondrial dyshomeostasis and neuronal cells injury. |
|---|---|
| المؤلفون: | Carvalho C; Center for Neuroscience and Cell Biology, University of Coimbra (CNC-UC), Portugal; Center for Innovation in Biomedicine and Biotechnology (CIBB), Portugal; Institute for Interdisciplinary Research (III), University of Coimbra, Portugal. Electronic address: cristina.im.carvalho@gmail.com., Moreira PI; Center for Neuroscience and Cell Biology, University of Coimbra (CNC-UC), Portugal; Center for Innovation in Biomedicine and Biotechnology (CIBB), Portugal; Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Electronic address: venta@ci.uc.pt. |
| المصدر: | Free radical biology & medicine [Free Radic Biol Med] 2024 Aug 01; Vol. 220, pp. 192-206. Date of Electronic Publication: 2024 May 09. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 8709159 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4596 (Electronic) Linking ISSN: 08915849 NLM ISO Abbreviation: Free Radic Biol Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Tarrytown, NY : Elsevier Science Original Publication: New York : Pergamon, c1987- |
| مواضيع طبية MeSH: | Lysine*/analogs & derivatives , Lysine*/metabolism , Mitochondria*/metabolism , Mitochondria*/pathology , Mitochondria*/drug effects , Neurons*/metabolism , Neurons*/pathology , Neurons*/drug effects , Reactive Oxygen Species*/metabolism , Organophosphorus Compounds*/pharmacology , Endoplasmic Reticulum Stress*/drug effects , Membrane Potential, Mitochondrial*/drug effects, Humans ; Cell Line, Tumor ; Cell Survival/drug effects ; Glycation End Products, Advanced/metabolism ; Homeostasis ; Antioxidants/pharmacology ; Antioxidants/metabolism ; Neuroblastoma/pathology ; Neuroblastoma/metabolism ; Piperidines |
| مستخلص: | Enhanced formation of advanced glycation end products (AGEs) is a pivotal factor in diabetes pathophysiology, increasing the risk of diabetic complications. Nε-carboxy-methyl-lysine (CML) is one of the most relevant AGEs found in several tissues including the peripheral blood of diabetic subjects. Despite recognizing diabetes as a risk factor for neurodegenerative diseases and the documented role of mitochondrial abnormalities in this connection, the impact of CML on neuronal mitochondria and its contribution to diabetes-related neurodegeneration remain uncertain. Here, we evaluated the effects of CML in differentiated SH-SY5Y human neuroblastoma cells. Due to the association between mitochondrial dysfunction and increased production of reactive oxygen species (ROS), the possible protective effects of MitoTempo, a mitochondria-targeted antioxidant, were also evaluated. Several parameters were assessed namely cells viability, mitochondrial respiration and membrane potential, ATP and ROS production, Ca 2+ levels, mitochondrial biogenesis and dynamics, mito/autophagy, endoplasmic reticulum (ER) stress and amyloidogenic and synaptic integrity markers. CML caused pronounced mitochondrial defects characterized by a significant decrease in mitochondrial respiration, membrane potential, and ATP production and an increase in ROS production. An accumulation of individual mitochondria associated with disrupted mitochondrial networks was also observed. Furthermore, CML caused mitochondrial fusion and a decrease in mitochondrial mass and induced ER stress associated with altered unfolded protein response and Ca 2+ dyshomeostasis. Moreover, CML increased the protein levels of β-secretase-1 and amyloid precursor protein, key proteins involved in Alzheimer's Disease pathophysiology. All these effects contributed to the decline in neuronal cells viability. Notable, MitoTempo was able to counteract most of CML-mediated mitochondrial defects and neuronal cells injury and death. Overall, these findings suggest that CML induces pronounced defects in neuronal mitochondria and ER stress, predisposing to neurodegenerative events. More, our observations suggest that MitoTempo holds therapeutic promise in mitigating CML-induced mitochondrial imbalance and neuronal damage and death. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: MitoTempo; Mitochondrial defects; Neurodegeneration; Neuroprotection; Nε-carboxymethyl lysine |
| المشرفين على المادة: | 70YDX3Z2O7 (N(6)-carboxymethyllysine) K3Z4F929H6 (Lysine) 0 (Reactive Oxygen Species) 0 (Organophosphorus Compounds) 0 (MitoTEMPO) 0 (Glycation End Products, Advanced) 0 (Antioxidants) 0 (Piperidines) |
| تواريخ الأحداث: | Date Created: 20240511 Date Completed: 20240526 Latest Revision: 20240526 |
| رمز التحديث: | 20240527 |
| DOI: | 10.1016/j.freeradbiomed.2024.05.011 |
| PMID: | 38734265 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-4596 |
|---|---|
| DOI: | 10.1016/j.freeradbiomed.2024.05.011 |