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Clinical Effects of Pollution
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
UCP2 is a member of a family of mitochondrial uncoupling proteins that are homologous to UCP1. Although UCP2 shares 60% sequence identity with UCP1 and both proteins localize to the IM, UCP2 exhibits a broad tissue distribution and is abundantly expressed in monocytes and macrophages,732 whereas UCP1 expression is restricted to brown adipose tissue. UCP2 has been shown to induce mild mitochondrial uncoupling, which increases the rate of respiration and is thought to reduce electron leak from oxidative phosphorylation complexes, thereby decreasing mitochondrial superoxide generation.733
Applications of Pluripotent Stem Cells in the Therapy and Modeling of Diabetes and Metabolic Diseases
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
Suranjit Mukherjee, Shuibing Chen
Thus, the fact that iPSCs are derived from patients with T2DM or forms of lipodystrophy holds enormous potential to reveal mechanisms and phenotypes that result in human adipocyte dysfunction via disease modeling. Currently, only a limited number of protocols to differentiate human PSCs to human adipocytes have been reported. Early studies for hES cell-derived adipocytes exhibited limited analysis on expression of maturity markers such as CEBPα as well as minimal characterization of functional properties, such as adiponectin and leptin secretion and glucose uptake in the presence of insulin (34,35). More recently, published studies have emerged demonstrating robust generation of white and brown adipocytes from hESCs using both lentiviral and growth factor cocktail-based differentiation strategies (36,37). The differentiation of white adipocytes from hESCs and iPSCs was achieved using lentiviral-based expression of PPARγ. At the end of the differentiation period, lipid-filled white adipocytes emerged, expressing maturity markers such as CEBPα, fatty acid binding protein 4, hormone-sensitive lipase, and lipoprotein lipase. The white adipocytes also demonstrated functional activities, including glycerol release, glucose uptake in the presence of insulin, and leptin and adiponectin secretion. Using the same lentiviral-based approach, brown adipocytes were derived from hESCs and iPSCs via overexpression of PPARγ, CEBPβ, and/or PRDM16. The derived brown adipocytes express maturity markers, such as uncoupling protein 1 (UCP1), PGC1α, and cytochrome c1 (CYC1), as well as functional properties, such as elevated oxygen consumption. The drawback of this lentiviral-based differentiation protocol is that it cannot be used to study the defects related to genes upstream of the PPARγ signaling pathway. The second reported protocol for brown adipocyte differentiation used embryoid bodies in a hemopoietin growth factor cocktail containing KIT ligand, FLT3 ligand, interleukin-6, vascular endothelial growth factor, insulin-like growth factor-2, and BMP4 and BMP7 in two different phases. The reported brown adipocytes expressed maturity markers such as UCP1, PGC1α, CIDEA, CYC1, ELOVL3, and proliferator-activated receptor-α. The transplantation of these brown adipocytes into mice demonstrated improved fasting blood glucose and triglyceride levels when compared to vehicle control.
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
PKA phosphorylates downstream MAPKs also named extracellular signal-regulated kinases (ERKs) mediate cell proliferation, differentiation, growth, and transcriptional regulation (Jain et al. 2018; Li et al. 2016; Takahashi et al. 2017). Data demonstrated that SN upregulated the expression of MAPK1 gene in both cell lines. MAPK1 translates ERK1 protein kinase, which is associated with the activation of biological functions, such as cell growth, adhesion, survival, and differentiation (Li, Tuergan, and Abulizi 2015). MAPK/ERKs participate in the transcriptional modulation of UCP1 (uncoupling protein 1) related to mitochondrial biogenesis during thermogenesis (Kohlie et al. 2017).