Lycium barbarum polysaccharide degrades the mutant huntingtin by ubiquitin-proteasome pathway
FANG Fang, CHEN Tian, PENG Yun-tao, LI He
Chinese Journal of Clinical Anatomy ›› 2017, Vol. 35 ›› Issue (6) : 641-644.
Lycium barbarum polysaccharide degrades the mutant huntingtin by ubiquitin-proteasome pathway
Objective To detect the degradation pathway of the mutant huntingtin (mHtt) after treating Lycium barbarum polysaccharide (LBP). Methods HEK293 cells that stably expressed mHtt containing 160 glutamine repeats was treated with LBP of various doses, CCK8 assay was used to detect the cell viability, and caspase-3 activity assay kit was used to detect the caspase-3 activity; the mHtt in HEK293-160Q cells was observed under fluorescence microscope after treatment with LBP and the images were analyzed by Image Pro Plus 6.0, at the same time, to detect its mRNA; LBP, MG132 and chloroquine were used to treat HEK293-160Q cells separately, and the changes of the mHtt were determined by Western Blot. Results LBP could increase the viability and decrease the caspase-3 activity in HEK293-160Q cells; LBP could reduce the mHtt and did not change its mRNA levels; after treating HEK293-160Q cells with the different medicines , the Western Blot results showed that compared to cells receiving only LBP treatment, the degeneration of mHtt was significantly reduced after treating LBP and MG132. No influence on mHtt after treating LBP and chloroquine was observed. Conclusions LBP can degrade the mHtt by ubiquitin-proteasome pathway, increase the cell viability and decrease the apoptosis by alleviating the cytotoxicity of mHtt.
Mutant huntingtin; Lycium barbarum polysaccharide; Ubiquitin-proteasome pathway;  / Autophagy-lysosome pathway
[1] Cattaneo E, Zuccato C, Tartari M. Normal huntingtin function: An alternative approach to huntington's disease [J]. Nat Rev Neurosci, 2005, 6(12): 919-930.
[2] A novel gene containing a trinucleotide repeat that is expanded and unstable on huntington's disease chromosomes. The huntington's disease collaborative research group [J]. Cell, 1993, 72(6): 971-983.
[3] Warby SC, Doty CN, Graham RK, et al. Activated caspase-6 and caspase-6-cleaved fragments of huntingtin specifically colocalize in the nucleus [J]. Hum Mol Genet, 2008, 17(15): 2390-2404.
[4] Ross CA, Aylward EH, Wild EJ, et al. Huntington disease: Natural history, biomarkers and prospects for therapeutics [J]. Nat Rev Neurol, 2014, 10(4): 204-216.
[5] Fang F, Peng T, Yang SM, et al. Lycium barbarum polysaccharide attenuates the cytotoxicity of mutant huntingtin and increases the activity of akt [J]. Int J Dev Neurosci, 2016, 52(4): 66-74.
[6] Menalled LB, Sison JD, Wu Y, et al. Early motor dysfunction and striosomal distribution of huntingtin microaggregates in huntington's disease knock-in mice [J]. J Neurosci, 2002, 22(18): 8266-8276.
[7] Imarisio S, Carmichael J, Korolchuk V, et al. Huntington's disease: From pathology and genetics to potential therapies [J]. Biochem J, 2008, 412(2): 191-209.
[8] Ayala-Pena S. Role of oxidative DNA damage in mitochondrial dysfunction and huntington's disease pathogenesis [J]. Free Radic Biol Med, 2013, 62(9): 102-110.
[9] Pelegri C, Duran-Vilaregut J, del Valle J, et al. Cell cycle activation in striatal neurons from huntington's disease patients and rats treated with 3-nitropropionic acid [J]. Int J Dev Neurosci, 2008, 26(7): 665-671.
[10]Li XJ, Li H, Li S. Clearance of mutant huntingtin [J]. Autophagy, 2010, 6(5): 663-664.
[11]Ciechanover A. Proteolysis: From the lysosome to ubiquitin and the proteasome [J]. Nat Rev Mol Cell Biol, 2005, 6(1): 79-87.
[12]Ciechanover A, Kwon YT. Degradation of misfolded proteins in neurodegenerative diseases: Therapeutic targets and strategies [J]. Exp Mol Med, 2015, 47(3): e147.
/
〈 |
|
〉 |