Vitamin K2 Modulates Organelle Damage and Tauopathy Induced by Streptozotocin and Menadione in SH-SY5Y Cells
Open Access
- 20 June 2021
- journal article
- research article
- Published by MDPI AG in Antioxidants
- Vol. 10 (6), 983
- https://doi.org/10.3390/antiox10060983
Abstract
Vitamin K2, known for its antioxidative and anti-inflammatory properties, can act as a potent neuroprotective molecule. Despite its action against mitochondrial dysfunction, the mechanism underlying the links between the protective effects of vitamin K2 and endoplasmic reticulum (ER) stress along with basal levels of total tau protein and amyloid-beta 42 (Aβ42) has not been elucidated yet. To understand the neuroprotective effect of vitamin K2 during metabolic complications, SH-SY5Y cells were treated with streptozotocin for 24 h and menadione for 2 h in a dose-dependent manner, followed by post-treatment of vitamin K2 for 5 h. The modulating effects of vitamin K2 on cell viability, lactate dehydrogenase release, reactive oxygen species (ROS), mitochondrial membrane potential, ER stress marker (CHOP), an indicator of unfolded protein response (UPR), inositol requiring enzyme 1 (p-IRE1α), glycogen synthase kinase 3 (GSK3α/β), total tau and Aβ42 were studied. Results showed that vitamin K2 significantly reduces neuronal cell death by inhibiting cytotoxicity and ROS levels and helps in the retainment of mitochondrial membrane potential. Moreover, vitamin K2 significantly decreased the expression of CHOP protein along with the levels and the nuclear localization of p-IRE1α, thus showing its significant role in inhibiting chronic ER stress-mediated UPR and eventually cell death. In addition, vitamin K2 significantly down-regulated the expression of GSK3α/β together with the levels of total tau protein, with a petite effect on secreted Aβ42 levels. These results suggested that vitamin K2 alleviated mitochondrial damage, ER stress and tauopathy-mediated neuronal cell death, which highlights its role as new antioxidative therapeutics targeting related cellular processes.This publication has 74 references indexed in Scilit:
- Streptozotocin-Induced Cytotoxicity, Oxidative Stress and Mitochondrial Dysfunction in Human Hepatoma HepG2 CellsInternational Journal of Molecular Sciences, 2012
- Induction of diabetes with signs of autoimmunity in primates by the injection of multiple-low-dose streptozotocinBiochemical and Biophysical Research Communications, 2011
- Lifelong Low-Phylloquinone Intake Is Associated with Cognitive Impairments in Old RatsJournal of Nutrition, 2011
- Glycogen synthase kinase-3 regulates endoplasmic reticulum (ER) stress-induced CHOP expression in neuronal cellsExperimental Cell Research, 2011
- Cerebral amyloid angiopathy in streptozotocin rat model of sporadic Alzheimer’s disease: a long-term follow up studyJournal of Neural Transmission, 2011
- Menadione triggers cell death through ROS-dependent mechanisms involving PARP activation without requiring apoptosisFree Radical Biology & Medicine, 2010
- Pathological roles of MAPK signaling pathways in human diseasesBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2010
- Neuronal cell death in neurodegenerative diseases: recurring themes around protein handlingJournal of Cellular and Molecular Medicine, 2008
- The Alzheimer's disease Beta-secretase enzyme, BACE1Molecular Neurodegeneration, 2007
- Adaptation to ER Stress Is Mediated by Differential Stabilities of Pro-Survival and Pro-Apoptotic mRNAs and ProteinsPLoS Biology, 2006