[논문]Neuregulin-1 inhibits CoCl 2 -induced upregulation of excitatory amino acid carrier 1 expression and oxidative stress in SH-SY5Y cells and the hippocampus of mice

Kim, Han-Byeol; Yoo, Ji-Young; Yoo, Seung-Yeon; Lee, Jun-Ho; Chang, Wonseok; Kim, Hye-Sun; Baik, Tai-Kyoung; Woo, Ran-Sook

doi:10.1186/s13041-020-00686-2

[해외논문] Neuregulin-1 inhibits CoCl 2 -induced upregulation of excitatory amino acid carrier 1 expression and oxidative stress in SH-SY5Y cells and the hippocampus of mice 원문보기

Molecular brain, v.13 no.1, 2020년, pp.153 -

Kim, Han-Byeol (Department of Anatomy and Neuroscience, College of Medicine, Eulji University, 143-5Jung-Gu, Yongdu-Dong, Daejeon, 301-746 Republic of Korea) , Yoo, Ji-Young (Department of Anatomy and Neuroscience, College of Medicine, Eulji University, 143-5Jung-Gu, Yongdu-Dong, Daejeon, 301-746 Republic of Korea) , Yoo, Seung-Yeon (Department of Anatomy and Neuroscience, College of Medicine, Eulji University, 143-5Jung-Gu, Yongdu-Dong, Daejeon, 301-746 Republic of Korea) , Lee, Jun-Ho (Department of Emergency Medical Technology, Daejeon University, Daejeon, 34520 Republic of Korea) , Chang, Wonseok (Department of Physiology, College of Medicine, Eulji University, Daejeon, 301-746 Republic of Korea) , Kim, Hye-Sun (Department of Pharmacology, College of Medicine, Seoul National University, Seoul, 110-799 Korea) , Baik, Tai-Kyoung (Department of Anatomy and Neuroscience, College of Medicine, Eulji University, 143-5Jung-Gu, Yongdu-Dong, Daejeon, 301-746 Republic of Korea) , Woo, Ran-Sook (Department of Anatomy and Neuroscience, College of Medicine, Eulji University, 143-5Jung-Gu, Yongdu-Dong, Daejeon, 301-746 Repub)

Abstract ▼ AI-Helper

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.

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