China
Africa
Explore chapters and articles related to this topic
Multiple Roles of Cardiac Metabolism: New Opportunities for Imaging the Physiology of the Heart
Published in Robert J. Gropler, David K. Glover, Albert J. Sinusas, Heinrich Taegtmeyer, Cardiovascular Molecular Imaging, 2007
The hypothesis finds further support by the observations that insulin promotes tolerance against ischemic cell death via the activation of issue-specific cell-survival pathways in the heart (73). Specifically, activation of PI3 kinase, a downstream target of the insulin receptor substrate (IRS), and activation of protein kinase B/Akt, are mediators of antiapoptotic, cardioprotective signaling through activation of p70s6 kinase and inactivation of proapoptotic peptides. The major mediator is Akt (or protein kinase B). Akt is located at the center of insulin and insulin-like growth factor 1 (IGF1) signaling. As the downstream serine-threonine kinase effector of PI3 kinase, Akt plays a key role in regulating cardiomyocyte growth and survival (74). Overexpression of constitutively active Akt raises myocardial glycogen levels and protects against ischemic damage in vivo and in vitro (75). Not surprisingly, Akt is also a modulator of metabolic substrate utilization (76). Phosphorylation of GLUT4 by Akt promotes its translocation and increases glucose uptake. Although the “insulin hypothesis” is attractive, there is also good evidence showing that the signaling cascade is dependent on the first committed step of glycolysis and translocation of hexokinase to the outer mitochondrial membrane (77,78). These few examples illustrate the fact that any signals detected by metabolic imaging of stressed or failing heart are the product of complex cellular reactions—truly only the tip of an iceberg.
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.
p-synephrine induces transcriptional changes via the cAMP/PKA pathway but not cytotoxicity or mutagenicity in human gastrointestinal cells
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Diego Luis Ribeiro, Ana Rita Thomazela Machado, Carla Machado, Alexandre Ferro Aissa, Patrick Wellington Dos Santos, Gustavo Rafael Mazzaron Barcelos, Lusânia Maria Greggi Antunes
The expression of genes related to the PI3K/AKT signaling pathway is stimulated not only by ERK mitogen-kinases but also by cAMP/PKA protein kinases (Huang et al. 2018). In this study, SN was shown to significantly upregulate expression of AKT1 (serine/threonine kinase 1), also named as protein kinase B (PKB) in MNP01 and Caco-2 cells. AKT1 is downstream in the PI3K pathway, and AKT1 (PKB) activation regulates many cellular processes, including metabolism, cell proliferation, survival, and inflammation (Gonzalez and McGraw 2009; Hirsch, Gulluni, and Martini 2020; Martini et al. 2014; Schultze et al. 2012).
Malignant growth of arsenic-transformed cells depends on activated Akt induced by reactive oxygen species
Published in International Journal of Environmental Health Research, 2023
Qun Lou, Fuxun Chen, Bingyang Li, Meichen Zhang, Fanshuo Yin, Xiaona Liu, Zaihong Zhang, Xin Zhang, Chenlu Fan, Yanhui Gao, Yanmei Yang
The most fundamental trait of malignant proliferative cells involves their ability to sustain chronic proliferation. Cancer cells and malignant proliferation cells always deregulate signals that instruct cell growth-and-division cycle, which ensures homeostasis of cell number and thus maintenance of normal tissue architecture and function. These signals control a variety of cell-biological aspects, including energy consumption, in addition to regulating cell cycle progression and cell proliferation. Akt, also known as protein kinase B (PKB), regulates a wide range of physiological and oncogenic processes such as cell growth, cell cycle progression, survival, migration, angiogenesis and energy metabolism reprogramming through binding and phosphorylating its downstream effectors(Cheng et al. 2005). Aberrant activation of the Akt signaling pathway is frequently observed in human cancers (Tokunaga et al. 2006; Shukla et al. 2007; Rho et al. 2011; Cui et al. 2012; Danielsen et al. 2015) and some malignant transformed cells (Sun et al. 2001; Morley et al. 2007; Pan et al. 2011). It has been shown that arsenite exposure enhanced phosphorylation of Akt(Ouyang et al. 2007; Li et al. 2015) in variety cell types and inhibition of Akt pathway by its dominant mutants markedly impaired the proliferation and cell transformation induced by arsenite exposure(Ouyang et al. 2007, 2008; Zhou et al. 2018). Activated Akt regulated cells progression in two ways: on the one hand, it regulated phosphorylation of GSK-3β/Cyclin D1 to accelerate the cell cycle process from G1 to S/G2M Phase after exposure to arsenite (Chen et al. 2019); on the other hand, low-dose arsenic causes the change from oxidative phosphorylation to glycolysis, which induced MEFs and A375 cells proliferation (Li et al. 2015). These results suggest that Akt activation might be required for arsenite-induced human cells transformation and proliferation. However, it is unclear whether activated Akt is indispensable for maintaining malignant phenotype.