Both nitric oxide and nitrite prevent homocysteine-induced endoplasmic reticulum stress and subsequent apoptosis via cGMP-dependent pathway in neuronal cells
| Autor: | Sung Hun Kim, Hyun-Ock Pae, Ju Hwan Lee, Hun-Taeg Chung, Seung Won Choi, Sun-Oh Jeong, Yong Son, Yong-Kwan Cheong |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty XBP1 Biophysics Apoptosis Nitric Oxide Biochemistry Nitric oxide Cell Line 03 medical and health sciences chemistry.chemical_compound Mice Annexin Internal medicine medicine Animals Nitrite Molecular Biology Cyclic GMP Homocysteine Nitrites Neurons Endoplasmic reticulum Cell Biology Endoplasmic Reticulum Stress Cytoprotection Cell biology 030104 developmental biology Endocrinology Neuroprotective Agents chemistry Unfolded protein response Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 493(1) |
| ISSN: | 1090-2104 |
| Popis: | Growing evidence indicates that endoplasmic reticulum (ER) stress and/or ER stress-mediated apoptosis may play a role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. The present study investigated the effects of non-cytotoxic concentrations of nitric oxide (NO) and nitrite, a metabolite of NO, on ER stress and ER stress-mediated apoptosis in Neuro-2a cells exposed to homocysteine (Hcy), an endogenous ER stress inducer. Hcy induced ER stress, as confirmed by inositol-requiring enzyme 1α (IRE1α) phosphorylation and X-box-binding protein-1 (Xbp1) mRNA splicing as well as C/EBP homologous protein (CHOP) expression, and apoptosis, as verified by Annexin V-positive cells. Surprisingly, non-cytotoxic NO (S-nitrosoglutathione) and nitrite markedly reduced Hcy-induced IRE1α phosphorylation, Xbp1 mRNA splicing, CHOP expression, and Annexin V-positive cells, indicating the cytoprotection of NO and nitrite against Hcy-induced ER stress and apoptosis. Moreover, inhibition of sGC/cGMP pathway abolished the cytoprotective effects of NO and nitrite, whereas cellular elevation of cGMP levels mimicked the cytoprotective actions of NO and nitrite. These findings provide the first evidence showing that both NO and nitrite can reduce ER stress and subsequent apoptosis via NO-sGC-cGMP pathway in neuronal cells and suggesting that NO and/or nitrite may have therapeutic value in the treatment of ER stress-associated neurodegenerative diseases. |
| Databáze: | OpenAIRE |
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