• Journal of Life Science
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• v.26 no.7
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• pp.868-874
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• 2016

Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 are members of the serine or threonine protein kinase superfamily that phosphorylates the hydroxyl group of serine or threonine through the highly conserved kinase region. The RIPK family plays a crucial role not only in inflammation and innate immunity, but also in mediating programmed cell death, such as apoptosis and necroptosis. The interaction between RIPK1 and other TNFR1-related proteins has been shown to assemble a signaling complex I that controls activation of the pro-survival transcription factor NF-κB upon binding of cytokines to TNF receptor 1 (TNFR1). Moreover, RIPK1 and RIPK3 interact through their RIP homotypic interaction motifs (RHIMs) to mediate programmed necrosis, which has long been considered an accidental and uncontrolled cell death form with morphological characteristics differing from those of apoptosis. Highly conserved sequences of RHIM in RIPK1 and RIPK3 were shown to regulate their binary interaction, leading to assembly of a cytosolic amyloid complex termed the “necrosome”. The necrosome also contains mixed lineage kinase domain-like protein (MLKL), which has been found recently to be a substrate of RIPK3 to mediate downstream signaling. This review provides an overview of the functional and physiological characteristics of RIPKs and MLKL in TNF signaling.

• Journal of Life Science
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• v.21 no.11
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• pp.1625-1630
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• 2011

Heme oxygenase-1 (HO-1) is a stress-responsive protein that is known to regulate cellular functions such as cell proliferation, inflammation, and apoptosis. In this study, we investigated the role of NADPH oxidase on the expression of HO-1 in human liver hepatoma cell line HepG2. Diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, markedly inhibited HO-1 expression and the nuclear translocation of transcription factor Nrf2 in cobalt protoporphyrin (CoPP) or hemin-treated HepG2 cells. Similarly, the knockdown of $p47^{phox}$, a cytosolic factor for NADPH oxidase activity, by siRNA inhibited the CoPP-induced expression of HO-1. In addition, GSHmee, an intracellular antioxidant, blocked the expression of HO-1 in CoPP-treated cells. Based on these results, we conclude that the blockage of NADPH oxidase with DPI or $p47^{phox}$ siRNA inhibits CoPP-induced HO-1 expression in HepG2 cells, and also suggest that the expression of HO-1 in CoPP-induced HepG2 cells is associated with increase of intracellular ROS by NADPH oxidase activity.

• Journal of Chest Surgery
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• v.35 no.1
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• pp.11-19
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• 2002

Background: Ischemia-reperfusion myocardial injury is an important factor to determine the early and the late mortality of transplanted patients. Recently, modulation of the cytosolic NADH/NAD+ ratio by Pyruvate and aspartate was tested to Protect the heart from ischemia-reperfusion injury. Material and Method: We added pyruvate and aspartate to the University of Wisconsin solution, and evaluated their effect on myocardial protection. We used 16 piglet(age 1 to 3 days) hearts. Eight hearts were arrested with and stored in the University of Wisconsin solution(UW solution) for 24 hours(control group), and the other eight hearts were arrested with and stored in the modified UW solution added pyruvate(3mmol/L) and aspartate(2 mmol/L)(test group). All hearts underwent modified reperfusion with blood cardioplegic solution followed by conversion to a left-sided working model with perfusion from a support pig. And then, we measured stroke work index(SWI), high-energy phosphate stores, and myocardial water content of the hearts. SWI was calculated at left ventricular end-diastolic pressures of 3, 6, 9, and 12 mmHg after 60 and 120 minutes reperfusion, respectively, Result: At 60 minutes and 120 minutes after reperfusion, SWI was higher in the test group than in the control group significantly. The levels of AMP, ADP, ATP of the test group were also higher. But, the creatine phosphate level and myocardial water content were similar in the two groups. Conclusion: From these results, we could Prove that pyruvate and aspartate enhance cardiac contractility and high-energy phosphate stores after ischemia.