Rapamycin prevents the mutant huntingtin-suppressed GLT-1 expression in cultured astrocytes
Lin, FangNote: Order does not necessarily reflect citation order of authors.
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CitationChen, Lei-lei, Jun-chao Wu, Lin-hui Wang, Jin Wang, Zheng-hong Qin, Marian Difiglia, and Fang Lin. 2012. “Rapamycin prevents the mutant huntingtin-suppressed GLT-1 expression in cultured astrocytes.” Acta Pharmacologica Sinica 33 (3): 385-392. doi:10.1038/aps.2011.162. http://dx.doi.org/10.1038/aps.2011.162.
AbstractAim: To investigate the effects of rapamycin on glutamate uptake in cultured rat astrocytes expressing N-terminal 552 residues of mutant huntingtin (Htt-552). Methods: Methods: Primary astrocyte cultures were prepared from the cortex of postnatal rat pups. An astrocytes model of Huntington's disease was established using the astrocytes infected with adenovirus carrying coden gene of N-terminal 552 residues of Huntingtin. The protein levels of glutamate transporters GLT-1 and GLAST, the autophagic marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the autophagy substrate p62 in the astrocytes were examined using Western blotting. The mRNA expression levels of GLT-1 and GLAST in the astrocytes were determined using Real-time PCR. 3H]glutamate uptake by the astrocytes was measured with liquid scintillation counting. Results: The expression of mutant Htt-552 in the astrocytes significantly decreased both the mRNA and protein levels of GLT-1 but not those of GLAST. Furthermore, Htt-552 significantly reduced 3H]glutamate uptake by the astrocytes. Treatment with the autophagy inhibitor 3-MA (10 mmol/L) significantly increased the accumulation of mutant Htt-552, and reduced the expression of GLT-1 and 3H]glutamate uptake in the astrocytes. Treatment with the autophagy stimulator rapamycin (0.2 mg/mL) significantly reduced the accumulation of mutant Htt-552, and reversed the changes in GLT-1 expression and 3H]glutamate uptake in the astrocytes. Conclusion: Rapamcin, an autophagy stimulator, can prevent the suppression of GLT-1 expression and glutamate uptake by mutant Htt-552 in cultured astrocytes.
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