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Mechanisms of Nanotoxicity to Cells, Animals, and Humans
Published in Vineet Kumar, Nandita Dasgupta, Shivendu Ranjan, Nanotoxicology, 2018
Belinda Wong Shu Ee, Puja Khanna, Ng Cheng Teng, Baeg Gyeong Hun
Apart from nutrient levels, the mTOR pathway is also influenced by insulin levels. Insulin stimulation activates the formation of phosphatidylinositol (3,4,5)-triphosphate (PIP3), which then phosphorylates protein kinase B (PKB)/Akt (Stokoe et al. 1997). Phosphorylated PKB/Akt, in turn, phosphorylates tuberous sclerosis complex 2 (TSC2), rendering TSC2 unable to interact with tuberous sclerosis complex 1 (TSC1) (Manning et al. 2002). Since TSC1/TSC2 complex cannot be formed, Ras homologue enriched in the brain (Rheb) remains in its active form and activates mTOR, which then downregulates autophagy genes (Zhang et al. 2003; Long et al. 2005). The mTOR pathway is one of the pathways that nanoparticles utilize to induce autophagy. It has been reported that SiNPs and iron oxide nanoparticles induce autophagy via the P13-K/Akt/mTOR pathway in HUVECs and A549 cells (Khan et al. 2012; Duan et al. 2014). Similarly, ZnO NPs and functionalized SWCNT also induced autophagosome accumulation and reduced Akt phosphorylation in Balb/c mice-derived macrophages and A549 cells, respectively. On top of that, introducing TSC2 siRNAs in the exposed A549 cells was shown to improve cell viability, indicating the significant role of TSC2 in activating autophagy (Liu et al. 2011; Roy et al. 2014a). Polyamidoamine dendrimer (PAMAM) also deregulated the Akt-TSC2-mTOR signaling pathway in A549 cells as characterized by LC3 aggregations and reduced Akt phosphorylation. Likewise, TSC2 inhibition successfully rescued the autophagic phenomenon (Li et al. 2009). From the numerous studies conducted, the P13-K/Akt/mTOR pathway was found to be the main signaling cascade activated upon nanoparticle exposure in cells, irrespective of the type of nanoparticles used.
Investigate the role of PIK3CA gene expression in colorectal polyp development
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Ameer Ali Imarah, Rana Ahmed Najm, Haider Ali Alnaji, Saleem Khteer Al-Hadraawy, Abbas F. Almulla, Hussein Raof Al-Gazali
The gene PIK3CA, encoding the alpha catalytic subunit of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), plays an important role in developing many malignancies. The PIK3CA gene is found at locus 3q26.32 on the long arm of chromosome number 3. PIK3CA mutations have been found in many malignancies, including the most common cancers, such as breast, endometrial, and colorectal cancers [23]. The PIK staining in the current study shows that all control group cases were negative, while in the patient’s group, all cases were positive, as shown in Figures (8–11). These results may indicate a possible role of the PIK3CA gene in tumor development, and these results are consistent with a study achieved by [24].