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MAPK signaling in spermatogenesis and male infertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Archana Devi, Bhavana Kushwaha, Gopal Gupta
The p38 mitogen-activated protein (MAP) kinases are serine-/threonine-based kinases composed of four members (p38α, p38β, p38γ and p38δ). These members show similarity in amino acid sequences, but their expression patterns are different (38). MAPK-p38 plays a key role in driving cellular activities in response to various extracellular stress stimuli. Interestingly, p38 MAPKs can also exert their function independent of its kinase activity, which it carries out by direct binding to its targets (39). Extracellular stress stimuli and inflammatory cytokines can also activate p38, which affects many biological activities downstream in the cell, such as inflammation, apoptosis, cell differentiation and the cell cycle (40). The upstream kinases MKK3 and MKK6 are responsible for p38 MAPK activation (41). Its activity is mainly controlled by phosphorylation-dephosphorylation mechanisms, and the duration of phosphorylation is pivotal in regulating cell fate (42). The MAP kinase-activated protein kinase 2 (MAPKAPK2 or MK2), the well-known substrate of MAPK p38, has been demonstrated to activate various transcription factors such as ATF1, c-Fos and c-Jun, which are reported to regulate steroid biosynthesis (43), and the molecular chaperone heat shock protein 27(Hsp27) that regulates actin dynamics to prevent its destabilization during stress (44). Besides MK2, Na+/H+ exchangers (NHE) are also reported as a substrate for p38MAPK, which ensures the spermatogenic event and the spermatozoal maturation by regulating pH and ionic balance (45,46).
Articular Cartilage Development
Published in Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi, Articular Cartilage, 2017
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi
The p38 protein has four distinct isoforms, α, β, γ, and δ (50% identity to ERK2 for p38α), with each of these isoforms having different substrate specificity. p38 is denoted by the presence of a conserved Thr-Gly-Tyr (TGY) sequence in the phosphorylation activation loop. p38 was initially identified as being activated by lipopolysaccharide (LPS) (Han et al. 1993, 1994). Common stimuli include environmental stresses, such as UV, oxidative stress, osmotic shock, hypoxia, mechanical loading, and inflammatory cytokines (interleukin 1 [IL-1], TNF-α), but rarely growth factors. Not surprisingly, given these activation stimuli, p38 plays a role in immune and inflammatory reactions, cell differentiation, and apoptosis.
Opioid Medications and Correct Medical Usage—An Update
Published in Gary W. Jay, Practical Guide to Chronic Pain Syndromes, 2016
The p38 mitogen-activated protein kinases (p38 MAPK) are signaling molecules, part of a family of serine/threonine protein kinases, which play a role in cellular responses to external stress signals. Inhibitors of two members of the p38 family have anti-inflammatory effects via inhibiting the expression of inflammatory mediators (89). Activation of p38 MAPK in spinal microglia mediates morphine antinociceptive tolerance. Minocycline, a selective inhibitor of microglia activation, has been reported to attenuate peripheral inflammation-induced hyperalgesia by inhibiting p38 MAPK in the spinal microglia. These authors demonstrated that minocycline antagonizes morphine antinociceptive tolerance, possibly due to the inhibition of p38 activation in spinal microglia (90).
Deer antler based active ingredients have protective effects on LPS/d -GalN-induced acute liver injury in mice through MAPK and NF-κB signalling pathways
Published in Pharmaceutical Biology, 2022
Guixiang He, Quanmin Zhao, Yan Zhao, Ying Zong, Shigang Gu, Mengjie Li, Renjie Li, Jiaxin Sun
More and more studies have shown that mitogen-activated protein kinase (MAPK) and nuclear factor kappa light chain enhancer activated B cells (NF-κB) can link inflammation with many diseases (Hilliard et al. 2020). The MAPK family plays a major role in regulating the production of iNOS and pro-inflammatory cytokines. For inflammation-related diseases, most investigators have studied three parallel subfamilies of ERK, p38 and JNK (Kim et al. 2013). In general, activation of p38 is necessary for the expression of many inflammatory molecules. The ERK pathway also plays an important role in regulating NO and a variety of cytokines (including TNF-α, IL-1β and IL-6). LPS/d-GalN stimulation will cause continuous JNK activation and translocation to mitochondria, leading to increased mitochondrial permeability conversion, and ultimately leading to liver cell death (Decker and Keppler 1974; He et al. 2014). In the current study, we evaluated the effects of R1 protein components on MAPKs pathway related proteins and iNOS proteins. The results showed that LPS/d-GalN induced phosphorylation of ERK, JNK and p38, significantly inhibiting iNOS protein expression.
The mechanism of miR-363-3p/DUSP10 signaling pathway involved in the gastric mucosal injury induced by clopidogrel
Published in Toxicology Mechanisms and Methods, 2021
Jiang Zongdan, Lu Yuyu, Wang Zhibing, Li Chao, Zhang Zhenyu, Sun Weihao
Our recent study (Wu et al. 2013) had concluded that attenuated expression of the TJ proteins occludin and ZO-1 in human gastric epithelial cells could be involved in clopidogrel-induced gastric mucosal injury through activation of the p38 MAPK pathway. P38 is a kinase that regulates multiple cellular functions, including cell apoptosis, differentiation, stress response, proliferation, and so on (Cuenda and Sanz-Ezquerro 2017). Negative regulation of MAPK activity is mediated by MAPK phosphatase (MKP) (Farooq and Zhou 2004). The dual-specificity phosphatase 10 (DUSP10) also called MKP5 was identified as a phosphatase that selectively inactivates JNK and p38 MAPK (Tanoue et al. 1999). Interestingly, different groups have described how the DUSP10 gene is negatively regulated by miRNAs, which are induced in different diseases and cancers. In hepatocellular cancer and pancreatic cancer, miR-181 and miR-92a, respectively, negatively regulate the DUSP10 expression, affecting the proliferation and migration of tumorigenic cells (Song et al. 2013; He et al. 2014).
Insights and controversies on sunscreen safety
Published in Critical Reviews in Toxicology, 2020
Juliana P. Paiva, Raiane R. Diniz, Alvaro C. Leitão, Lucio M. Cabral, Rodrigo S. Fortunato, Bianca A. M. C. Santos, Marcelo de Pádula
ZnO nanoparticles (20 nm) can trigger apoptosis of human dermal fibroblasts via the p53-p38 pathway, which is activated by genotoxic stress and leads to cell cycle arrest or apoptosis. p38 is a MAP-kinase protein that, when activated, enhances p53 phosphorylation and its activity (Meyer et al. 2011). In its turn, p53 can regulate antioxidant genes to diminish ROS-damage induced by ZnO treatments (Borrás et al. 2011). Different studies have reported the cytotoxic effects of the ZnO nanoparticles on many mammalian cell types, like skin epidermal, neuroblastoma, vascular endothelial, neural, alveolar epithelial, and neural stem cells (Jeng and Swanson 2006; Gojova et al. 2007; Lai et al. 2008; Deng et al. 2009). In addition, ZnO increases mRNA levels of inflammatory markers like IL-8 in human aortic endothelial cells (Gojova et al. 2007), induces clastogenic effects in Chinese hamster ovary cell strain (Dufour et al. 2006), is cytotoxic for human CD4 + T cells, (Reddy et al. 2007), and causes the inhibition of seed germination and root growth (Lin and Xing 2007).