Bibliographic Details
| Title: |
Neuregulin-1 inhibits CoCl2-induced upregulation of excitatory amino acid carrier 1 expression and oxidative stress in SH-SY5Y cells and the hippocampus of mice. |
| Authors: |
Kim, Han-Byeol1 (AUTHOR), Yoo, Ji-Young1 (AUTHOR), Yoo, Seung-Yeon1 (AUTHOR), Lee, Jun-Ho2 (AUTHOR), Chang, Wonseok3 (AUTHOR), Kim, Hye-Sun4,5 (AUTHOR), Baik, Tai-Kyoung1 (AUTHOR) tkbaik@eulji.ac.kr, Woo, Ran-Sook1 (AUTHOR) rswoo@eulji.ac.kr |
| Source: |
Molecular Brain. 11/13/2020, Vol. 13 Issue 1, p1-16. 16p. |
| 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. [ABSTRACT FROM AUTHOR] |
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