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Chemopreventive Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
NF-κB is a major transcription factor which tightly controls DNA transcription, cell survival, and immune responses to infection, and controls many genes involved in inflammatory processes. Up-regulated expression of NF-κB is common in chronic inflammation which can promote the initiation of cancer. Some chemopreventive agents are thought to work by down-regulating NF-κB expression thus leading to cellular protection from DNA damage caused by inflammation. Another example is Nrf2, a dual-specificity phosphatase that plays a key role in inactivating several MAP kinase isoforms during inflammatory processes. Some chemopreventive agents are thought to work by inhibiting NF-κB or Nrf2.
Bannayan–Riley–Ruvalcaba Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Gabriela Maria Abreu Gontijo, Clóvis Antônio Lopes Pinto
The PTEN gene (also known as TEP1 [TGF-b regulated and epithelial cell-enriched phosphatase], or MMAC1 [mutated in multiple advanced cancers]) is located on chromosome 10q23.31 and contains nine exons that span a genome distance of >120 kb [1]. Its coding sequence of 1209-bp is predicted to generate a 403-aa, 47 kDa dual-specificity phosphatase (PTEN), which consists of two major functional domains, an N-terminal domain from exons 1–6 and a C-terminal domain from exons 6–9.
Molecular basis and biomarkers of disease activity
Published in Seema Chopra, Endometriosis, 2020
Several previous studies in the literature have evaluated expression in the endometrial cells among patients with endometriosis. Researchers have shown at least 72 dysregulated genes in women with endometriosis by sequencing mRNA from the secretory phase endometrial samples. Of these, 4 upregulated proteins including MMP-11, Fos proto-oncogene, dual specificity phosphatase and serpin family E member 1, and adenosine deaminase 2 were validated using quantitative polymerase chain reaction (PCR). Similarly, several acyl carnitines were found to be elevated while trimethylamine-N-oxide was decreased in the cases of endometriosis using mass spectrometry methods. Studies using nuclear magnetic resonance spectrometry have revealed that metabolites containing valine, fucose, and choline, amino acids lysine/arginine, and lipoproteins were upregulated, while creatinine was downregulated in patients with late stages of the disease [41].
Targeting endoplasmic reticulum stress—the responder to lipotoxicity and modulator of non-alcoholic fatty liver diseases
Published in Expert Opinion on Therapeutic Targets, 2022
Yu Luo, Qiangqiang Jiao, Yuping Chen
FFAs-stimulated ER stress was found to induce nuclear transglutaminase 2 and activate both apoptosis inducing factors and cytochrome c release in hepatocytes via PERK pathway [83]. Several studies supported the function of CHOP in ER stress-induced hepatocyte death [13,30]. SFAs-triggered ER stress and apoptosis in human liver cell were enacted through the PERK/ATF4/CHOP signaling pathway [13] that either increased the expression of DR5 or activated hepatic NLRP3 inflammasome in a CHOP-dependent manner [1,30]. Especially, it was the activation of PERK-CHOP but not IRE1 or ATF6 by ER stress that induced dual-specificity phosphatase 5 (DUSP5) in hepatocytes and livers to suppress extracellular-signal-regulated kinase (ERK) signaling and cleave caspase-3[84]. In addition, CHOP cooperated with activator protein (AP-1) to mediate p53 upregulated modulator of apoptosis (PUMA) induction during hepatocyte lipoapoptosis [30]. The anti-apoptotic activity of IL-24, the deletion of which incurred more cell death in the CCl4-challenged mouse livers or TM-treated hepatocytes, was also relied on an intact eIF2α-CHOP pathway [85]. However, the ATF4-CHOP-GADD34 pathway appeared to be impaired in the livers of NAFLD patients [33]; an elevated CHOP expression did not accompany with more pro-apoptotic Bcl-2 antagonist killer 1 (BAK) and Bcl-2 associated x protein (BAX) in the livers of NAFLD patients administered with ursodeoxycholic acid (UDCA) [86]. These findings emphasize that the role of CHOP in liver injury may alter with certain threshold too.
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).
New insights into the novel anti-inflammatory mode of action of glucocorticoids
Published in Immunopharmacology and Immunotoxicology, 2020
Deepa K. Ingawale, Satish K. Mandlik
It is also called as Dual specificity phosphatase 1 (DUSP1). It is member of phosphatases family that catalyzes the removal of phosphate group from threonine, serine or tyrosine amino acid residues [110]. It is an inducible nuclear phosphatase that dephosphorylates Mitogen-activated protein kinases (MAPKs) [111]. MKP-1 proteins are important regulators of immune responses and inflammatory process and were found to regulate p38 MAPK and JNK signaling [112]. MKP-1 proteins are activated by phosphorylation process and linked to many physiological and pathophysiological processes, such as CNS disorders, skeletal muscle metabolism, malignancy, atherosclerosis, asthma, psoriasis and rheumatoid arthritis [113–119]. The GC-induced expression of MKP-1 has also been associated with inhibition of extracellular signal-regulated kinase (ERK) pathway in certain cells [120]. The phosphorylation of transcription factors and RNA-binding proteins regulates the expression of inflammatory gene at both transcriptional and post-transcriptional levels [121]. MKP-1 is induced by pro-inflammatory stimuli and forms a negative feedback loop to limit MAPK signaling and the expression of inflammatory mediators. Hence, over expression of MKP-1 protein attenuates JNK and p38 MAPK pathways signaling and inhibits the expression of several inflammatory genes [122,123].