Upregulation of glutamate transporter 1 by mTOR/Akt pathway in astrocyte culture during oxygen-glucose deprivation and reoxygenation.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0043312 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1106 (Electronic) Linking ISSN: 00144819 NLM ISO Abbreviation: Exp Brain Res Subsets: MEDLINE

Original Publication: Berlin : Springer Verlag

Proto-Oncogene Proteins c-akt*/metabolism ; Oxygen*; Humans ; Up-Regulation ; Astrocytes/metabolism ; Glucose/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Amino Acid Transport System X-AG/metabolism ; Cells, Cultured

Astrocyte-specific glutamate transporter subtype 1 (GLT-1) plays an important role in influencing glutamate excitatory toxicity and preventing the death of excitatory toxic neurons. Although the mammalian target of rapamycin (mTOR)/protein kinase B(Akt)/nuclear factor kappa B signaling cascade is involved in the upregulation of astrocytic GLT-1 in oxygen-glucose deprivation (OGD), it is unclear whether the mTOR/Akt pathway is involved in astrocytic GLT-1 upregulation in OGD and reoxygenation (OGD/R). In this study, we found that the treatment of cultured astrocytes with rapamycin and triciribine led to the decreased astrocytes' protrusions, smaller nuclei, and an increased apoptotic rate. The inhibitors of mTOR complex 1 significantly increased the expression levels of phosphorylated Akt-Ser473 (p-Akt), phosphorylated Akt-Thr308(p-Akt), and GLT-1, while Akt-specific inhibitors blocked GLT-1 expression, suggesting that the mTOR/Akt pathway is involved in GLT-1 upregulation. We further demonstrated that astrocytes under OGD/R adapted to environmental changes through the mTOR/Akt pathway, mainly by altering cell morphology and apoptosis and upregulating the expression levels of p-Akt and GLT-1. Our results suggested that astrocytes may adapt to short-term ischemic-reperfusion injury by regulating cell morphology, apoptosis and GLT-1 upregulation.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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81870966 National Outstanding Youth Science Fund Project of National Natural Science Foundation of China

Keywords: Astrocytes; GLT-1; OGD/R; Rapamycin; p-Akt

EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
S88TT14065 (Oxygen)
IY9XDZ35W2 (Glucose)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
0 (Amino Acid Transport System X-AG)
EC 2.7.1.1 (MTOR protein, human)

Date Created: 20221127 Date Completed: 20230125 Latest Revision: 20230201

20231215

10.1007/s00221-022-06514-4

36436003