Downregualtion of dynamin-related protein 1 attenuates glutamate-induced excitotoxicity via regulating mitochondrial function in a calcium dependent manner in HT22 cells
| Autor: | Jun Su, Xianrui Yuan, Qing Liu, Haoyu Li, Yiwei Liao, Xiangyu Wang, Chi Zhang, Zijin Zhao, Shu-shan Sang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Dynamins
Biophysics Excitotoxicity Down-Regulation Glutamic Acid Apoptosis Biology Mitochondrion medicine.disease_cause Biochemistry Neuroprotection Mitochondrial apoptosis-induced channel Cell Line Mice DNM1L medicine Animals RNA Small Interfering Molecular Biology Glutamate receptor Cell Biology Molecular biology Mitochondria Cell biology Mitochondrial permeability transition pore Calcium Mitochondrial fission |
| Zdroj: | Biochemical and Biophysical Research Communications. 443:138-143 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2013.11.072 |
| Popis: | Glutamate-mediated excitotoxicity is involved in many acute and chronic brain diseases. Dynamin related protein 1 (Drp-1), one of the GTPase family of proteins that regulate mitochondrial fission and fusion balance, is associated with apoptotic cell death in cancer and neurodegenerative diseases. Here we investigated the effect of downregulating Drp-1 on glutamate excitotoxicity-induced neuronal injury in HT22 cells. We found that downregulation of Drp-1 with specific small interfering RNA (siRNA) increased cell viability and inhibited lactate dehydrogenase (LDH) release after glutamate treatment. Downregulation of Drp-1 also inhibited an increase in the Bax/Bcl-2 ratio and cleavage of caspase-9 and caspase-3. Drp-1 siRNA transfection preserved the mitochondrial membrane potential (MMP), reduced cytochrome c release, enhanced ATP production, and partly prevented mitochondrial swelling. In addition, Drp-1 knockdown attenuated glutamate-induced increases of cytoplasmic and mitochondrial Ca2+, and preserved the mitochondrial Ca2+ buffering capacity after excitotoxicity. Taken together, these results suggest that downregulation of Drp-1 protects HT22 cells against glutamate-induced excitatory damage, and this neuroprotection may be dependent at least in part on the preservation of mitochondrial function through regulating intracellular calcium homeostasis. |
| Databáze: | OpenAIRE |
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