Activation of AMPK pathway compromises Rab11 downregulation-mediated inhibition of Schwann cell proliferation in a Glut1 and Glut3-dependent manner. (16th February 2020)

• Record Type: Journal Article
• Authors: Li, Fan; Du, Wei; Wang, Hui; Zhao, Song; Zhu, Lin; Hao, Jun
• Is Part Of: Neuroscience letters. Volume 720(2020)
• Publication Date: 2020-02-16
• Subjects: Rab11 -- Proliferation -- AMPK -- Glut1 -- Glut3 -- Schwann cells; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2020.134762
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Rab11 downregulation inhibited the proliferation of rat Schwann cells. AMPK pathway activation ameliorated Rab11 downregulation-mediated inhibition of rat Schwann cell proliferation. Rab11 downregulation activated AMPK pathway by reducing Glut1 and Glut3 expression. Abstract: Rab11, a small GTPase, is an important protein in the regulation of intracellular plasma membrane trafficking. Schwann cells are the main cells of peripheral nerves and knockdown of Rab11 in these cells inhibits the formation of functional tunneling nanotubes (TNTs). However, the role of Rab11 in the functioning of Schwann cells remains elusive. Herein, using cell viability analysis, live/dead cell staining, BrdU assay, and western blot analysis with an AMPK antibody, we observed that the knockdown of Rab11 significantly inhibited the proliferation of RSC96 cells. Further investigations showed that the AMPK pathway was activated by the knockdown of Rab11, as indicated by the enhanced levels of phosphorylated AMPK. Moreover, suppression of AMPK pathway with Compound C aggravated Rab11 knockdown-induced inhibition of cell proliferation. In contrast, activation of the AMPK pathway with AICAR ameliorated the Rab11 knockdown-mediated inhibition of cell proliferation. Furthermore, the levels of Glut1 and Glut3 were decreased in the RSC96 cells upon Rab11 knockdown. Additionally, the knockdown of Glut1 and Glut3 led to the activation of the AMPK pathway in RSC96 cells. We conclude that the knockdown of Rab11 suppresses the proliferation of RSC96 cells, and as a compensatory mechanism, the activation of AMPK pathway, in a Glut1 and Glut3-dependent manner, improves RSC96 cell proliferation.