HomeIngredientCurcumin Inhibits Cell Damage and Apoptosis Caused by Thapsigargin-Induced Endoplasmic Reticulum Stress Involving the Recovery of Mitochondrial Function Mediated by Mitofusin-2

Curcumin Inhibits Cell Damage and Apoptosis Caused by Thapsigargin-Induced Endoplasmic Reticulum Stress Involving the Recovery of Mitochondrial Function Mediated by Mitofusin-2

February 22, 2022

Neurotox Res. 2022 Feb 22. doi: 10.1007/s12640-022-00481-y. Online ahead of print.

ABSTRACT

Endoplasmic reticulum stress (ERS) and mitochondrial dysfunction have been suggested to relate with the pathology of Alzheimer’s disease (AD). However, their cross-talk is needed to investigate further. Mitofusin-2 (Mfn2) is a member of mitochondria-associated membrane (MAM), which connects endoplasmic reticulum (ER) and mitochondria. This study investigated the protective effect of curcumin on thapsigargin (TG)-induced ERS and cell apoptosis and the role of Mfn2 on mitochondrial dysfunction. The cell viability of SH-SY5Y cells was decreased and cell damage and apoptosis were increased in a concentration-dependent manner when cells were treated with TG. TG upregulated the protein levels of GRP78, pSer981-PERK, and pSer51-eIF2α. Curcumin attenuated TG-induced damage on cell viability and apoptosis and downregulated the protein levels of GRP78, pSer981-PERK, and pSer51-eIF2α. TG caused the increases in intracellular reactive oxygen species (ROS) and in the protein levels of pSer40-Nrf2 and hemoglobin oxygenase 1 (HO-1). Curcumin decreased the TG-induced intracellular ROS but did not alter the protein levels of pSer40-Nrf2 and HO-1. TG resulted in the upregulation on Mfn2 expression and mitochondrial spare respiratory capacity but the downregulation on mitochondrial basal respiration and ATP production. Curcumin attenuated the TG-induced Mfn2 expression and mitochondrial stress. When Mfn2 was silenced by shRNA interference, curcumin failed to recovery the TG-damaged mitochondrial function. In general, the TG-induced ERS trigged mitochondrial dysfunction and cell apoptosis. Curcumin attenuates TG-induced ERS and the cell damage and apoptosis. Mfn2 is required for curcumin’s protection against the TG-induced damage on mitochondrial functions.

PMID:35192145 | DOI:10.1007/s12640-022-00481-y

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About The Author

Patrick Blanchard MD

Meet Dr. Blanchard Dr. Blanchard’s medical practice is an embodiment of Integrative health which brings conventional and complementary approaches together in a coordinated way. Conveniently located in sunny Florida and over the internet with ValiseMD’s secure HIPPA compliant telXmed servers. Since 1994, patients with a wide range of challenging medical problems have achieved optimum health using the best of natural medicine, judiciously combined with high-tech innovations. Breakthroughs are often achieved even after patients have consulted mainstream specialists and holistic practitioners. Dr. Blanchard is founder and CEO of ValiseMD, Inc. He is board certified in Family Medicine since 1994 and awarded Fellow of the American Academy of Family Physicians in 2001. He received the ‘Teacher of the Year’ award from the University of Kansas School of Medicine at completion of his residency in Family Medicine. He completed a fellowship at Wake Forest University in the field of vascular neurosonology. He holds a medical patent in the field of Gastroenterology. He holds an unrestricted license to practice medicine and surgery in Florida. He started his medical career as a Emergency Medical Technician, then as a Paramedic and later a Medical Doctor.