11/29/2023 0 Comments Jnk1 regulate jun protein turnover![]() ![]() (D) Cells transfected with either scramble or JNK1/2 siRNA I (100 nM) were evaluated for the levels of p-c-jun and c-jun. (C) RINm5F cells were transfected with scramble or JNK1/2 siRNA I (25–100 nM), and after 36 h, cells were lysed and the levels of JNK1/2 determined by Western blot analysis. On termination of incubation, cells were collected, and the levels of total and phospho-JNK1/2 (A) and Bip and CHOP (B) were evaluated by Western blot and quantitative RT-PCR, respectively. RINm5F cells were incubated with IL-1β (2 ng/ml) for 2, 4, 8, 12, and 24 h. IL-1β–mediated JNK1/2 activation precedes ER stress induction. This suggests a regulatory role of JNK1/2 in modulating the ER-mitochondrial-Ca(2+) axis by IL-1β in apoptotic cell death. This is accompanied by IL-1β-induced apoptosis, which is prevented by JNK1/2 siRNA and the IP3R inhibitor xestospongin C. All these events are prevented by JNK1/2 small interfering RNA (siRNA), indicating the mediating role of JNK1/2 in IL-1β-induced cellular alteration. Our results show that in RINm5F cells and human primary β-cells, IL-1β alters mitochondrial membrane potential, mitochondrial permeability transition pore opening, ATP content, and reactive oxygen species production and these alterations are preceded by ER Ca(2+) release via IP3R channels and mitochondrial Ca(2+) uptake. Because the ER is the organelle responsible for Ca(2+) handling and storage, here we examine the effects of IL-1β on cellular Ca(2+) movement and mitochondrial dysfunction and evaluate the role of JNK1/2. However, the detailed regulatory mechanisms are not completely understood. In earlier work we showed that JNK1/2 activation is initiated before ER stress and apoptotic induction in response to IL-1β. Elevated interleukin-1β (IL-1β) induces apoptosis in pancreatic β-cells through endoplasmic reticulum (ER) stress induction and subsequent c-jun-N-terminal kinase 1/2 (JNK1/2) activation. ![]()
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