Neuroprotective Effect of Tricyclic Pyridine Alkaloids from Fusarium lateritium SSF2, against Glutamate-Induced Oxidative Stress and Apoptosis in the HT22 Hippocampal Neuronal Cell Line
- Authors
- Lee, D.; Choi, H.G.; Hwang, J.H.; Shim, S.H.; Kang, K.S.
- Issue Date
- Nov-2020
- Publisher
- MDPI AG
- Keywords
- Apoptosis; Ca2+; Fusarium lateritium SSF2; Glutamate; HT22 cells; Oxidative stress
- Citation
- Antioxidants, v.9, no.11, pp.1 - 15
- Journal Title
- Antioxidants
- Volume
- 9
- Number
- 11
- Start Page
- 1
- End Page
- 15
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/79216
- DOI
- 10.3390/antiox9111115
- ISSN
- 2076-3921
- Abstract
- 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′-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′,7′-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–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′-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′-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′-anhydrooxysporidinone. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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