Neuroprotective Effect of Tricyclic Pyridine Alkaloids from Fusarium lateritium SSF2, against Glutamate-Induced Oxidative Stress and Apoptosis in the HT22 Hippocampal Neuronal Cell Line
| Autor: | Sang Hee Shim, Hyun Gyu Choi, Dahae Lee, Ji Hye Hwang, Ki Sung Kang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
HT22 cells Physiology Clinical Biochemistry glutamate medicine.disease_cause Biochemistry Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine oxidative stress Ca2+ Propidium iodide Molecular Biology Membrane potential biology Superoxide Cytochrome c lcsh:RM1-950 apoptosis Depolarization Cell Biology Molecular biology Fusarium lateritium SSF2 030104 developmental biology lcsh:Therapeutics. Pharmacology chemistry Apoptosis 030220 oncology & carcinogenesis biology.protein Intracellular Oxidative stress |
| Zdroj: | Antioxidants Volume 9 Issue 11 Antioxidants, Vol 9, Iss 1115, p 1115 (2020) |
| ISSN: | 2076-3921 |
| DOI: | 10.3390/antiox9111115 |
| Popis: | Excessive glutamate damages neuronal cells via the accumulation of intracellular reactive oxygen species (ROS), calcium ion (Ca2+) influx, depolarization of mitochondrial membrane potential, and apoptosis, which may result in the development of chronic neurodegenerative diseases. In this study, we evaluated the effects of 4,6&prime anhydrooxysporidinone isolated from endophytic fungus Fusarium lateritium SSF2 on glutamate-induced cytotoxicity, accumulation of intracellular ROS, increases in superoxide anion production, Ca2+, depolarization of mitochondrial membrane potential, and apoptotic cell death in hippocampal HT22 cells. 2&prime 7&prime Dichlorofluorescin diacetate (H2DCFDA) staining was used to determine the intracellular reactive oxygen species concentration and dihydroethidine (DHE) staining was used to determine the superoxide radical. Expression of the nuclear factor-erythroid-2&ndash related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was analyzed by Western blot. Fluo-4 staining was used to determine the intracellular Ca2+ levels. In order to explore mitochondrial membrane potential, tetramethylrhodamine methyl ester (TMRM) staining was used. Apoptotic cell death was evaluated using Annexin-V/propidium iodide (PI) staining and TUNEL staining. Expression of the cytochrome c release and cleaved caspase-9, -3 was analyzed by Western blot. Here, we were able to isolate 4,6&prime anhydrooxysporidinone from endophytic fungus, Fusarium lateritium SSF2, which was shown to protect HT22 cells from glutamate-induced cytotoxicity, accumulation of intracellular ROS, increases in superoxide anion production, Ca2+, and depolarization of mitochondrial membrane potential. In addition, 4,6&prime anhydrooxysporidinone enhanced the expressions of Nrf2 and HO-1. It also inhibited the apoptotic cell death through the inhibition of cytochrome c release and cleaved caspase-9, -3 in glutamate-treated HT22 cells. Therefore, our results provide ample evidence of the neuroprotective properties of 4,6&prime anhydrooxysporidinone. |
| Databáze: | OpenAIRE |
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