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Signalling Pathways in The Regulation of Cellular Responses to Exercise
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Anders Gudiksen, Stine Ringholm, Henriette Pilegaard
p38 has been shown to directly phosphorylate three different serine residues on PGC-1α, increasing PGC-1α activity in vitro (2), as well as to phosphorylate activating transcription factor 2 (ATF2) and MEF2, thus also promoting PGC-1α transcription (2, 76). ATF2 is a member of the CREB/ATF family of transcription factors that binds to the PGC-1α promoter and induces its transcription (Figure 8.2). Prolonged exercise (marathon running) has been shown to increase p38 and ERK1/2 phosphorylation together with enhancing DNA binding of MEF2 in human SkM (137). Moreover, it has been demonstrated that binding of ATF2 and MEF2 to PGC-1α increases 3 hours into recovery from an exercise bout (107), which may lead to transcription of genes encoding oxidative proteins (22, 105). In addition, MEF2 associated with HDAC5 decreased (indicating a nuclear export of HDAC5 and increased transcription) and MEF2 associated with PGC-1α increased in human SkM in response to 1 hour of moderate-intensity exercise (76) (Figure 8.2). Taken together, this establishes a firm connection between exercise-induced p38 regulation and regulation of mitochondrial biogenesis (Figure 8.2).
The Endothelium in Leukocyte Recruitment
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
As mentioned above, activation of the endothelium with inflammatory cytokines or certain endotoxin results in a striking increase in leukocyte adhesion under static or fluid flow conditions in vitro. This increase in adhesion is correlated with the expression of multiple adhesion molecules and chemotactic factors by the endothelium (reviewed in (9,11,12)). It is hypothesized that the leukocyte selectivity and temporal pattern of recruitment is the result of regulated expression of specific adhesion molecules and chemoattractants by the endothelium at sites of inflammation. Studies of the promotor regions of certain of these genes indicated that cytokines can induce synergistic interactions among a small group of transactivating factors, such as NF-κB and ATF-2/c-Jun, to form specialized complexes that activate transcription of certain genes [(38) and references therein]. In particular, incubation of endothelium with inflammatory cytokines (TNF-α, IL-1β) and certain gram-negative bacterial endotoxin dramatically induced the expression of E-selectin and VCAM-1, while that of ICAM-1 increased severalfold Similarly, the genes encoding leukocyte subset specific chemoattractants, such as interleukin-8 (IL-8) and monocyte-chemoattractant protein-1 (MCP-1), which are members of the chemokine gene family [reviewed in (13)], are also dramatically induced by the above inflammatory cytokines (11,12). Subsequent chapters examine members of the chemokine family involved in both basophil and eosinophil recruitment in vivo and in vitro.
Uterine fibroids and the endometrium
Published in Carlos Simón, Linda C. Giudice, The Endometrial Factor, 2017
Deborah E. Ikhena, Serdar E. Bulun
Depending on their size, uterine fibroids can place tremendous stress and stretch on the nearby myometrium and overlying endometrium. Fibroids are characterized by increased deposition of ECM, which accounts for most of their size. Fibroids express higher levels of AKAP13, which activates Rho and is associated with the cytoskeleton of fibroid cells (67). Additionally, expression of the stress response gene, activating transcription factor 3 (ATF3), is altered in the presence of uterine fibroids (68). Data suggest that there is abnormal communication between the external mechanical environment and RhoA-mediated reorganization of the actin cytoskeleton in fibroid cells (69).
Lactiplantibacillus plantarum 299v supplementation modulates β-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free BioBreeding rats
Published in Gut Microbes, 2022
Pinar Sargin, Mark F. Roethle, Shuang Jia, Tarun Pant, Ashley E. Ciecko, Samantha N. Atkinson, Nita H. Salzman, Ru-Jeng Teng, Yi-Guang Chen, Susanne M. Cabrera, Martin J. Hessner
Exposure of β-cells to cytokines and chronic inflammation disrupts endoplasmic reticulum (ER) homeostasis, promotes the accumulation of unfolded/misfolded protein, and triggers the unfolded protein response (UPR).11 The UPR is activated through three sensor proteins: protein kinase RNA-like ER kinase (Perk), activating transcription factor 6 (Atf6), and inositol requiring kinase-1α (Ire1α). The UPR promotes recovery and survival by arresting translation to reduce ER input, increasing chaperone expression to enhance protein folding capacity, enhancing antioxidative stress responses, and upregulating transcription of the ER-associated protein degradation (ERAD) and autophagy pathways to respectively foster removal of misfolded proteins and protein aggregates from the ER. Chronic hyperactivation of the UPR induces apoptosis.11
Lessons learned from the discovery and development of the sesquiterpene lactones in cancer therapy and prevention
Published in Expert Opinion on Drug Discovery, 2022
Israa A. Cheikh, Chirine El-Baba, Ali Youssef, Najat A. Saliba, Akram Ghantous, Nadine Darwiche
MAPK pathways represent ubiquitous signal transduction routes governed by multifunctional proline-directed serine/threonine (ProXSer/ThrPro) kinases (ERK, JNK, and p38). The latter enzymes regulate cell fate, proliferation, differentiation, homeostasis, and migration [176]. Extensive research demonstrated that aberrant MAPK signaling pathway activation plays a key role in the initiation, development, and progression of carcinogenesis [176]. Ultraviolet-B (UVB) irradiation is a well-known carcinogen that induces JNK and p38 activation in the established tumors [177,178]. Additionally, MAPK activation elicited by UVB exposure in cancer cells triggers c-Jun and Activating transcription factor 2 protein phosphorylation which induces ‘Activator protein-1’ (AP-1) activation. The latter plays a central role in neoplastic transformation in vitro and in vivo, and abrogating its effect is an attractive strategy in cancer chemoprevention [179]. Pretreatment of JB6 cells with parthenolide prior to UVB exposure remarkably suppressed UVB-induced JNK and p38 phosphorylation which blocked AP-1 activation [180].
Arsenic: an emerging role in adipose tissue dysfunction and muscle toxicity
Published in Toxin Reviews, 2022
Kaviyarasi Renu, Aditi Panda, Balachandar Vellingiri, Alex George, Abilash Valsala Gopalakrishnan
Arsenic mediates the endoplasmic stress to impede the process of adipogenesis. Arsenic activates the UPR by the inositol-requiring protein-1 (IRE-1); Activating transcription factor 6 (ATF6) and PKR-like ER kinase (PERK) genes (Oh et al.2012). The transcription factors involved in the regulation of the ER stress are C/EBP homologous protein (CHOP1), X-Box Binding Protein 1 (XBP-1); Activating Transcription Factor 4 (ATF4), and Activating Transcription Factor 6 (ATF6) (Oyadomari and Mori 2004). The inhibition of adipogenesis occurs with the dimerization of CHOP1 and C/EBP. Arsenic attenuates the differentiation of the adipogenesis activity via a decreased level of the Peroxisome Proliferator-activated receptor γ (PPAR-γ) and CCAAT-enhancer-binding proteins (C/EBPα). Arsenic exposure decreases the expression of the genes involved in adipogenesis, such as PPAR-γ, CEBPα, Retinoid X receptor-alpha (RXRα), Lipoprotein lipase (LPL), adipose differentiation-related protein (Adrp), Sterol regulatory element-binding protein (SREBP1), and adipsin with the increased CHOP10, an endoplasmic stress protein (Hou et al.2013). This further leads to toxicity in the adipose tissue.