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Neurodegeneration in Diabetes Mellitus
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Narsingh Verma, Smriti Rastogi
JNKs regulate various processes, such as brain development, repair, and memory formation, and are activated in response to a wide range of cellular stresses, as well as in response to inflammatory mediators. In fact, the JNK signaling pathway is induced by stress such as heat shock, UV irradiation, inflammation, and oxidative stress. Moreover, the translocation of JNK into mitochondria can result in impairment of energy metabolism.41 As a result, they are also potent effectors of neuroinflammation and neuronal death.42
Pathogenesis: Molecular mechanisms of osteoporosis
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
Anastasia E. Markatseli, Theodora E. Markatseli, Alexandros A. Drosos
RANKL binds to the osteoclast cell-surface receptor RANK. Subsequently, RANK is trimerized and recruits a member of the TNF receptor-associated factors (TRAFs) at specific sites within its cytoplasmic domain (167). These factors are TRAF 2, 5, and 6. The most basic factor for osteoclasts (precursors and mature) seems to be TRAF 6 (56,168). The signaling pathways that are activated after the binding of RANK with TRAF are as follows: Four pathways that induce the formation of osteoclasts: (a) inhibitor of NF-κB kinase (IKK)/NF-κB), (b) nuclear factor of activated T cells (NFATc1), (c) c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1), and (d) c-myc.Three pathways that mediate activation ([a] MKK6/p38/MITF and [b] Src) and survival of osteoclasts ([a] kinase pathway regulated by extracellular signal and [b] Src pathway) (169). Figure 2.2a summarizes the signal transduction pathways after RANK.
Postimplantation diabetic embryopathy
Published in Moshe Hod, Lois G. Jovanovic, Gian Carlo Di Renzo, Alberto de Leiva, Oded Langer, Textbook of Diabetes and Pregnancy, 2018
Ulf J. Eriksson, Parri Wentzel
The family of JNKs has three isoforms, JNK1, JNK2, and JNK3, where JNK1 and JNK2 are found in all cells and tissues and JNK3 is found in the brain, heart, and testes. JNK is activated by several stress stimuli, e.g., changes in levels of ROS, ultraviolet radiation, inflammatory signals, and protein synthesis inhibitors. JNK phosphorylates and thereby modifies the activity of several mitochondrial and nuclear proteins. Downstream molecules that are activated by JNK include c-Jun and p53. By activating and inhibiting other cellular proteins, JNK thus regulates cell growth, differentiation, survival, and apoptosis.
Advances in autophagy as a target in the treatment of tumours
Published in Journal of Drug Targeting, 2022
Yingying Li, Shan Gao, Xiyou Du, Jianbo Ji, Yanwei Xi, Guangxi Zhai
Aiming at regulation of Beclin1, there are three manners. Firstly, the competitive binding between BH3 analogues and BH3 domain inhibits the interaction between Beclin1 and Bcl-2 [171]. ABT-737 [172] is a BH3 analogue, which blocks the binding of Beclin1 with Bcl-2 and Beclin1 with Bcl-XL complex, and induces autophagy. Secondly, studies offer a latent adjustable solutions that JNK dissociates Bcl from Beclin1 and induce autophagy, which could be activated by bone morphogenetic protein 4 (BMP4), as a member of transforming growth factor - β (TGF - β) superfamily [101]. In prostate cancer, docetaxel could activate JNK, separate Bcl from Beclin1 and induce autophagy [102]. On the contrary, DJ-1 [115] inhibits the phosphorylation of NK and Bcl-2 so Beclin1 and Bcl-2 complex can’t be split and inhibit autophagy. The reported JNK inhibitors include SP600125, AS601245, JNK-IN-1, BI-78D3 [118]. Finally, some agents are expected to act directly on Beclin1 or VPS34, for example, SAR405 [173] and Autophinib [174] target VPS34 and inhibit autophagy and Arsenic trioxide and vitamin D3 [104] could directly stimulate Beclin1 to induce autophagy.
miR-128 regulated the proliferation and autophagy in porcine adipose-derived stem cells through targeting the JNK signaling pathway
Published in Journal of Receptors and Signal Transduction, 2021
Pengfei Gao, Haizhen Wang, Juan Liu, Yiqi Wu, Wei Hei, Zhiqiang He, Chunbo Cai, Xiaohong Guo, Guoqing Cao, Bugao Li
The c-Jun N-terminal kinase (JNK) signaling plays an important role in inflammation and apoptosis [11]. JNKs have a close relationship with c-Jun which is a kind of phosphorylation-activated transcription factor. JNKs consist of three encoded genes Jnk1, Jnk2 and Jnk3 in human. Jnk1 and Jnk2 are highly expressed in human tissues and Jnk3 is mainly expressed in the brain, heart and testis tissues. JNKs can be triggered by a variety of stressors such as oxidative stress and ultraviolet (UV) irradiation, resulting in cell apoptosis and growth inhibition [12]. Translation of JNK proteins from cytoplasm to nucleus induces activation of c-Jun [13], thus regulating the expression of apoptosis related genes, including B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) [14,15]. The JNK pathway is also the target of miRNAs [16,17]. However, the effects of miR-128-JNK on porcine adipose-derived stem cells (ASCs) remain uncertain.
Magnesium isoglycyrrhizinate ameliorates concanavalin A-induced liver injury via the p38 and JNK MAPK pathway
Published in Immunopharmacology and Immunotoxicology, 2020
Yudi Gao, Yuan Tian, Xiangying Zhang, Xiaohui Zhang, Zhongping Duan, Feng Ren, Yu Chen
Hepatic inflammatory responses are dependent on various cellular signaling pathways. The MAPK pathway is an important signal transduction system in eukaryotic cells, mediating intracellular responses to extracellular response signals. It is thought to be a key pathway that regulates and controls cellular inflammatory responses, inducing the expression of downstream apoptotic proteins including Bax, Bcl-2, and caspase-3, leading to apoptosis [12]. The MAPK pathway includes four subfamilies, Erk1/2, JNK, p38, and Erk5. Erk is widely distributed in various tissues and is involved in the regulation of cell proliferation, differentiation, and growth [32]. JNK is a key molecule in signal transduction induced by various stressors and is involved in the cellular response to radiation, osmotic pressure, temperature changes, and toxic substances. In addition, p38 mediates inflammation and apoptosis and is the target of a variety of anti-inflammatory drugs [33]. Studies have shown that many drugs can attenuate inflammation-induced liver injury via the MAPK signaling pathway, decreasing pro-inflammatory cytokine secretion [32]. Furthermore, MgIG attenuates LPS-induced hepatic inflammation by modulating the MAPK signaling pathway [33]. Our results showed that the administration of ConA stimulated the activation of JNK, and p38MAPK. However, the phosphorylation of JNK and p38 was blocked by pretreatment with MgIG (Figure 4). Therefore, the anti-inflammatory effect of MgIG is related to regulation of the MAPK signaling pathway.