Accelerating the clearance of mutant huntingtin protein aggregates through autophagy induction by europium hydroxide nanorods

Wei, Pengfei; Zhang, Li; Nethi, Susheel Kumar; Barui, Ayan Kumar; Lin, Jun; Zhou, Wei; Shen, Yi; Man, Na; Zhang, Yunjiao; Xu, Jing; Patra, Chitta Ranjan; Wen, Longping

doi:10.1016/j.biomaterials.2013.10.024

Cited by 66 publications

(52 citation statements)

References 58 publications

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“…Under normal physiological conditions, the cellular autophagic activity is maintained at a basal level, but can be markedly upregulated by nutrient starvation [11], chemical reagents [12] or other stimuli. So far, autophagy induction by major classes of nanomaterials, such as carbon-based nanomaterials [13e16], metal-based nanomaterials [17e20], rare earth oxides nanomaterials [21,22], polymer nanomaterials [23,24] and semiconductor QDs in different cell types has been reported [25e27]. There are several plausible mechanisms of autophagy induction by nanomaterials, the most popular ones involve oxidative stress [28,29] or damage of cellular organelles [30].…”

Section: Introductionmentioning

confidence: 99%

A real-time documentation and mechanistic investigation of quantum dots-induced autophagy in live Caenorhabditis elegans

et al. 2015

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Section: Introductionmentioning

confidence: 99%

A real-time documentation and mechanistic investigation of quantum dots-induced autophagy in live Caenorhabditis elegans

et al. 2015

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“…Recent studies demonstrate that the induction of autophagy by the RNA interference or some drugs improves the degradation of protein aggregates. The results suggest that the modification of autophagy activity may become a therapeutic tool of neurodegenerative disorders [9][10][11][12][13]. The intracellular controlled release of nucleic acids with from the nanospheres of a release carrier was effective in maintaining the biological activity 5 for a prolonged time period [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Intracellular release of rapamycin from poly (lactic acid) nanospheres modifies autophagy

Nagata

Matsui

Tabata

2016

Journal of Biomaterials Science, Polymer Edition

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The objective of this study is to investigate the autophagy activity of cells by the intracellular release of rapamycin (Rapa) of an autophagy inducer. Rapa was incorporated into nanospheres of poly (lactic-co-glycolic acid) (PLGA) for the controlled release of Rapa. Rapa was released from the PLGA nanospheres incorporating rapamycin (Rapa-PLGA-NS) with time while the Rapa-PLGA-NS were hydrolytically degraded. When human hepatocellular carcinoma (HepG2) cells were incubated with the Rapa-PLGA-NS, the Rapa-PLGA-NS were internalized, and the intracellular concentration was maintained over four days, indicating the intracellular Rapa release. The microtubule-associated protein 1 light chain (LC3) of an autophagy marker was significantly high for the Rapa-PLGA-NS group compared with the free Rapa group even after four days incubation. In addition, intracellular harmful ubiquitinated proteins were degraded by the intracellular release of Rapa even after four days incubation in contrast to free Rapa. It is concluded that the intracellular Rapa release is effective in modulating the autophagy activity over a longer time period.

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“…Autophagy can induce both cell survival and cell death under nutrient starvation, tumorigenesis including breast cancer,15 neurodegeneration, and other physiological and pathological processes 16,17. The conversion of LC3-I to LC3-II reflects the occurrence of autophagy 18. Two relatively well-established pathways that regulate autophagy contain the mTOR and IP3 cascades.…”

Section: Introductionmentioning

confidence: 99%

Gemcitabine resistance in breast cancer cells regulated by PI3K/AKT-mediated cellular proliferation exerts negative feedback via the MEK/MAPK and mTOR pathways

Yang¹,

Lin²,

Guo³

et al. 2014

OTT

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Chemoresistance is a major cause of cancer treatment failure and leads to a reduction in the survival rate of cancer patients. Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen-activated protein kinase (MAPK) pathways are aberrantly activated in many malignant tumors, including breast cancer, which may indicate an association with breast cancer chemoresistance. In this study, we generated a chemoresistant human breast cancer cell line, MDA-MB-231/gemcitabine (simplified hereafter as “231/Gem”), from MDA-MB-231 human breast cancer cells. Flow cytometry studies revealed that with the same treatment concentration of gemcitabine, 231/Gem cells displayed more robust resistance to gemcitabine, which was reflected by fewer apoptotic cells and enhanced percentage of S-phase cells. Through the use of inverted microscopy, Cell Counting Kit-8, and Transwell assays, we found that compared with parental 231 cells, 231/Gem cells displayed more morphologic projections, enhanced cell proliferative ability, and improved cell migration and invasion. Mechanistic studies revealed that the PI3K/AKT/mTOR and mitogen-activated protein kinase kinase (MEK)/MAPK signaling pathways were activated through elevated expression of phosphorylated (p)-extracellular signal-regulated kinase (ERK), p-AKT, mTOR, p-mTOR, p-P70S6K, and reduced expression of p-P38 and LC3-II (the marker of autophagy) in 231/Gem in comparison to control cells. However, there was no change in the expression of Cyclin D1 and p-adenosine monophosphate-activated protein kinase (AMPK). In culture, inhibitors of PI3K/AKT and mTOR, but not of MEK/MAPK, could reverse the enhanced proliferative ability of 231/Gem cells. Western blot analysis showed that treatment with a PI3K/AKT inhibitor decreased the expression levels of p-AKT, p-MEK, p-mTOR, and p-P70S6K; however, treatments with either MEK/MAPK or mTOR inhibitor significantly increased p-AKT expression. Thus, our data suggest that gemcitabine resistance in breast cancer cells is mainly mediated by activation of the PI3K/AKT signaling pathway. This occurs through elevated expression of p-AKT protein to promote cell proliferation and is negatively regulated by the MEK/MAPK and mTOR pathways.

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Accelerating the clearance of mutant huntingtin protein aggregates through autophagy induction by europium hydroxide nanorods

Cited by 66 publications

References 58 publications

A real-time documentation and mechanistic investigation of quantum dots-induced autophagy in live Caenorhabditis elegans

A real-time documentation and mechanistic investigation of quantum dots-induced autophagy in live Caenorhabditis elegans

Intracellular release of rapamycin from poly (lactic acid) nanospheres modifies autophagy

Gemcitabine resistance in breast cancer cells regulated by PI3K/AKT-mediated cellular proliferation exerts negative feedback via the MEK/MAPK and mTOR pathways

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