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Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel.
- Source :
-
Scientific reports [Sci Rep] 2020 Apr 15; Vol. 10 (1), pp. 6449. Date of Electronic Publication: 2020 Apr 15. - Publication Year :
- 2020
-
Abstract
- Hypoxia (HYPX) induced-overload Ca <superscript>2+</superscript> entry results in increase of mitochondrial oxidative stress, inflammation and apoptosis in several neurons. Ca <superscript>2+</superscript> permeable TRPM2 channel was gated by ADP-ribose (ADPR) and reactive oxygen species (ROS), although its activity was modulated in HYPX-exposed neurons by resveratrol (RSV). The aim of this study was to evaluate if a therapy of RSV can modulate the effect of HYPX in the TRPM2 expressing SH-SY5Y neuronal and HEK293 (no expression of TRPM2) cell lines. The SH-SY5Y and HEK293 cells were divided into four groups as control, RSV (50 μM and 24 hours), and HYPX and RSV + HYPX. For induction of HYPX in the cells, CoCl <subscript>2</subscript> (200 μM and 24 hours) incubation was used. HYPX-induced intracellular Ca <superscript>2+</superscript> responses to TRPM2 activation were increased in the SH-SY5Y cells but not in the HEK293 cells from coming H <subscript>2</subscript> O <subscript>2</subscript> and ADPR. RSV treatment improved intracellular Ca <superscript>2+</superscript> responses, mitochondrial function, suppressed the generation of cytokine (IL-1β and TNF-α), cytosolic and mitochondrial ROS in the SH-SY5Y cells. Intracellular free Zn <superscript>2+</superscript> , apoptosis, cell death, PARP-1, TRPM2 expression, caspase -3 and -9 levels are increased through activating TRPM2 in the SH-SY5Y cells exposed to the HYPX. However, the values were decreased in the cells by RSV and TRPM2 blockers (ACA and 2-APB). In SH-SY5Y neuronal cells exposed to HYPX conditions, the neuroprotective effects of RSV were shown to be exerted via modulation of oxidative stress, inflammation, apoptosis and death through modulation of TRPM2 channel. RSV could be used as an effective agent in the treatment of neurodegeneration exposure to HYPX.
- Subjects :
- Adenosine Diphosphate Ribose metabolism
Cell Hypoxia drug effects
Cell Hypoxia immunology
Cell Line, Tumor
Cobalt toxicity
HEK293 Cells
Humans
Hydrogen Peroxide metabolism
Hypoxia, Brain drug therapy
Hypoxia, Brain immunology
Hypoxia, Brain pathology
Mitochondria metabolism
Mitochondria pathology
Neurons cytology
Neurons immunology
Neurons pathology
Oxidative Stress drug effects
Oxidative Stress immunology
Resveratrol therapeutic use
Apoptosis drug effects
Mitochondria drug effects
Neurons drug effects
Resveratrol pharmacology
TRPM Cation Channels metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 32296107
- Full Text :
- https://doi.org/10.1038/s41598-020-63577-5