Autor: |
Han-Byeol Kim, Ji-Young Yoo, Seung-Yeon Yoo, Jun-Ho Lee, Wonseok Chang, Hye-Sun Kim, Tai-Kyoung Baik, Ran-Sook Woo |
Jazyk: |
angličtina |
Rok vydání: |
2020 |
Předmět: |
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Zdroj: |
Molecular Brain, Vol 13, Iss 1, Pp 1-16 (2020) |
Druh dokumentu: |
article |
ISSN: |
1756-6606 |
DOI: |
10.1186/s13041-020-00686-2 |
Popis: |
Abstract Excitatory amino acid carrier 1 (EAAC1) is an important subtype of excitatory amino acid transporters (EAATs) and is the route for neuronal cysteine uptake. CoCl2 is not only a hypoxia-mimetic reagent but also an oxidative stress inducer. Here, we found that CoCl2 induced significant EAAC1 overexpression in SH-SY5Y cells and the hippocampus of mice. Transient transfection of EAAC1 reduced CoCl2-induced cytotoxicity in SH-SY5Y cells. Based on this result, upregulation of EAAC1 expression by CoCl2 is thought to represent a compensatory response against oxidative stress in an acute hypoxic state. We further demonstrated that pretreatment with Neuregulin-1 (NRG1) rescued CoCl2-induced upregulation of EAAC1 and tau expression. NRG1 plays a protective role in the CoCl2-induced accumulation of reactive oxygen species (ROS) and reduction in antioxidative enzyme (SOD and GPx) activity. Moreover, NRG1 attenuated CoCl2-induced apoptosis and cell death. NRG1 inhibited the CoCl2-induced release of cleaved caspase-3 and reduction in Bcl-XL levels. Our novel finding suggests that NRG1 may play a protective role in hypoxia through the inhibition of oxidative stress and thereby maintain normal EAAC1 expression levels. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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