JNK signaling cascade

Pyne, S., Chapman, J., Steele, L. and Pyne, N.J., 1996, Sphingomyehn-derived lipids differentially regulate the extracellular signal-regulated kinase 2 (ERK-2) and c-Jun N-terminal kinase (JNK) signal cascades in airway smooth muscle. Ear. J. Biochem. 237 819-826. 

Sarker KP, Biswas KK, Yamakuchi M, Lee KY, Hahiguchi T, Kracht M, Kitajima 1, Maruyama I (2003) ASKl-p38 MAPK/JNK signaling cascade me ates anandamide-induced PC12 cell death. J Neurochem 85 50-61... 

Barker, K.P, Biswas, K.K.,Yamakuchi, M., Lee, K.Y., Hahiguchi,T., Kracht, M. etal. (2003) ASKl-p38MAPK/JNK signaling cascade mediates anandamide-induced PC12 cell death. Journal of Neurochemistry 85 50-61. 

The EC-SOD content is very low compared to other SODs in parenchymal cells. However, because it is known that adipose tissue has a moderately high content of EC-SOD, EC-SOD might have an important protective role as an anti-inflammatory factor. In this study, we demonstrated that the expression of EC-SOD was co-regulated with adiponectin through TNF-a and JNK signaling cascades. From these observations, it is speculated that the reduction of EC-SOD by hypoxic conditions is similar to adiponectin and leads to a decrease in the resistance to oxidative stress. Overall, it is speculated that the reduction of EC-SOD leads to decreased resistance to oxidative stress and accelerates ROS-derived diseases, and prevents the reduction of EC-SOD, contributing to the control of redox homeostasis under hypoxic conditions. 

Pretreatment of neurons by flavonoids (epicatechin and its 3 -D-methylether, kaempferol) strongly inhibits cell death induced by oxidized low-density lipoproteins (ox-LDL) without reduction of ox-LDL uptake or intracellular oxidative stress. Cell protection is selectively correlated to inactivation of JNK, thus suggesting that, irrespective of their H-atom donating activity, flavonoids can selectively attenuate a pro-apoptotic signaling cascade involving MAPKs. 

Fig. 3.4 The JNK/SAPK signaling pathway various signals including cytokines activate the MAP kinases. The JNK/SAPK cascade is activated in response to inflammatory cytokines, heat shock or ultraviolet radiation. Two small G proteins, Rac and cdc42, mediate the activation of the MAP kinases. After activation, cdc42 binds to and activates PAK65 protein kinase. This results in the activation of MEKK, which eventually phosphorylates JNK/SAPK that migrates to the nucleus and activates the expression of several genes specifically the phosphorylation of c-Jun (see Color Insert)...

Fig. 3. Possible intracellular signaling cascade involved in regulation of cyclooxygenase (COX)-2 expression. Abbreviations AP-1, activator protein 1 ERK, extracellular signal-regulated protein kinase IkB, inhibitory Bk JNK, c-Jun NHj-terminal kinase MAPK, mitogen-activated protein kinase MKK, mitogen-activated protein kinase kinase NFkB, nuclear factor-KB NIK, NF-KB-inducing kinase PKC, protein kinase C TPA, 12-O-tetradecanoylphorbol-13-acetate ROS, reactive oxygen species UV, ultraviolet light.

As a result of the diversity of stimuh and upstream events that lead to the activation of JNKs, this signaling cascade is complex and not completely understood. Furthermore, the essential Ca Vcalmodulin binding to the neuron-specific... 

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