Nano Material Induced Protective Autophagy And Roles Of MiRNAs In Nano Material Induced Autophagy

Autophagy is a highly conserved cellular selective degradation progress, removing damaged organelles and misfolded or aggregated proteins, as well as intercellular pathogens. Autophagy begins with engulfing substrate with phagophore to form autophagosome. Autophagosome is then delivered to lysosome, where autolysome is formed by the fusing of autophagosome with lysosome. Autophagy plays very important roles in a variety kinds of physiological and pathological processes, such as maintainance of cell homeostasis, embryo development, nutrient deficiency, neurodegenerative disorders and cancer etc.. It is widely reported that a variety of nano materials have the capacity of inducing autophagy. Autophagy is currently considered to be an iconic biological response of organic or inorganinc nano materials. Gold related nano particles, metal oxides nano particles, quantum dots, nano fullerene and its derivatives, rare earth oxides nano crystals, PAMAM and liposomes are shown to have the ability of inducing autophagy. Autophagy elicited by nano-sized materials is commonly believed to contribute to cell death. This cell death promoting effect provides possibilities to use nano materials in bio-medical applications. Nano fullerenes are found to have chemosensitization capabilities and have potentials in cancer chemotherapies. However, these negative effects of nano materials also become a major obstacle of using nano materials in living organisms. The study of nano materials induced autophagy is not yet mature; many of them are focused on phenomenal research. Currently, results about biological effects caused by nano materials on the organisms on signaling pathway level or transcription level are still quite rare.In this dissertation, we represent some systematic research on autophagy induced by two kinds of nano-sized materials:nano paramontroseite VO2(nano P-VO2) and water soluble nano fullerenes.Protective autophagy triggered by nano P-VO2in HeLa cell lines is reported here for the first time. All the other nanomaterial-induced autophagic responses reported so far are detrimental to cell fate, but our work on nano P-VO2provided an interesting exception. Furthermore, the significance of ROS generation is also revealed here. Another celluar effect of nano P-VO2was causing overexpression of heme oxygenase-1(HO-1) in HeLa cells. A specific inhibitor of autophagy,3MA, restrained the overexpression of HO-1. Yet the HO-1inhibitor, Znpp, which impaired the viability of cells undergoing nano P-VO2treatment, had no affects on autophagy triggered by nano P-VO2. On the other hand, Y2O3nano crystals, which act as a control material in this study, did not alt the expression of HO-1while inducing death-promoting autophagy in HeLa cells. All these results suggested that P-VO2induced a novel nanomaterials-induced cyto-protective autophagy, likely through up-regulation of HO-1.hi previous reports of our group, water soluble nano fullerene (nano C60) is proved to have the capacity of inducing autophagy. Here, by using high throughtput miRNA microarray technology, we indicated that miRNA is involved in the autophagic response in HeLa cells treated with nano C60. Further efforts on transfection of specific inhibitors or mimics of miRNAs showed that hsa-miR-4324and hsa-miR-24have crucial part to play in nano C60initiated autophagy. This work is a brand new attemption of nanomterial-induced autophagy on a post-transcriptional level.Two works in this dissertation revealed new research aspects in nano-material induced autophagy and provide helpful hints for related research in the future.