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Affect of the Small Molecule and Nanogold on Autophagy

Author: WuYanYang
Tutor: YuLi
School: Tsinghua University
Course: Biology
Keywords: Gold nanoparticles 3-MA Vps34
CLC: R363
Type: PhD thesis
Year: 2012
Downloads: 9
Quote: 0
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Abstract


Autophagy is a conserved degradation process misfolded or aggregated proteinsand damaged organelles are engulfed by special double membrane vesicles termedautophagosome and subsequencetly delivered to lysosome for degradation and playsimportant pathophysiological roles.3-methyladenine (3-MA) is widely used inautophagic research although a few inhibitors of autophagy are in market. Theefficiency is very low when the concentration is lower than10mM and solubility ispoor in water, which impedes the progress of being widely used in Clinic research.3-MA is6-amino-3-methyl purine, it is blended by the pyrimidine and imidazole ring,pyrimidine and imidazole form the ring system.It can be easily modified at C6and N3poisition. Here we designed and synthesized36derivatives of3-MA. After screeningwith high-throughput system, we identified3small molecues had the inhibitory abilityand further confirmed it by immunoflurorescence staining. We also identified that1mM20,24and34inhibited autophagy, especially34, completely inhibited autophagy in theconcentration of50μM. These new inhibitors of autophagy provide useful tools tostudy the cellular role of the autophagy and may lead to the development of therapeuticagents for the treatment of various diseases.It has been reported that nanoparticles caninduce autophagy. Gold nanoparticle is one of being widely used in biomaterial andbiotechnology. In this paper we found that nanogold entered into NRK cells by thesize-dependent manner. Nano gold caused lysosome alkalinization and blocked thedegradation of autophagosome. So it should be cautious to use nanoparticles fordiseases treatment.

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