1.Study of level and functions of P-type ATPase7B in hepatic cells of patients with hepatolenticular degeneration
Daping LV ; Yongzhu HAN ; Xun WANG
Journal of Clinical Neurology 1993;0(03):-
Objective To explore the level and main functions of P-type ATPase7B in hepatic cells of patients with hepatolenticular degeneration(HLD).Methods The hepatic cells from 5 normal controls and 9 patients with HLD were cultured in vitro. P-type ATPase7B levels in hepatic cells were examined and compared by SDS-PAGE and Western-blot techniques.Results Compared with the controls, 9 patients displayed various changes of electrophoresis strip. Almost normal strips at 155?103 were found in 3 cases, no strip was found in 1 case, and thinner and lighter strips were showed in the remain 5 cases. 6 cases presented abnormal specific reaction strips.Conclusion Mutations of gene ATPase7B in HLD patients cause change of P-type ATPase7B in quantity and quality, thus leads to dysmetabolism of copper.
2.The Nedd8-activating enzyme inhibitor MLN4924 suppresses colon cancer cell growth via triggering autophagy.
Yongzhu LV ; Bing LI ; Kunna HAN ; Yang XIAO ; Xianjun YU ; Yong MA ; Zhan JIAO ; Jianjun GAO
The Korean Journal of Physiology and Pharmacology 2018;22(6):617-625
Neddylation is a post-translational protein modification process. MLN4924 is a newly discovered pharmaceutical neddylation inhibitor that suppresses cancer growth with several cancer types. In our study, we first investigated the effect of MLN4924 on colon cancer cells (HCT116 and HT29). MLN4924 significantly inhibited the neddylation of cullin-1 and colon cancer cell growth in a time and dose-dependent manner. MLN4924 induced G2/M cell cycle arrest and apoptosis in HCT116 and HT29 cells. Moreover, MLN4924 also triggered autophagy in HCT116 and HT29 cells via suppressing the PI3K/AKT/mTOR pathway. Inhibiting autophagy by autophagy inhibitor 3-MA or ATG5 knockdown reversed the function of MLN4924 in suppressing colon cancer cell growth and cell death. Interestingly, MLN4924 suppresses colon cell growth in a xenograft model. Together, our finding revealed that blocking neddylation is an attractive colon cancer therapy strategy, and autophagy might act as a novel anti-cancer mechanism for the treatment of colon cancer by MLN4924.
Apoptosis
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Autophagy*
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Cell Cycle Checkpoints
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Cell Death
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Colon*
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Colonic Neoplasms*
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Heterografts
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HT29 Cells
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Humans
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Protein Processing, Post-Translational