Urinary Trypsin Inhibitors Afford Cardioprotective Effects through Activation of PI3K-Akt and ERK Signal Transduction and Inhibition of p38 MAPK and JNK

Abstract

Background: We determined the effect of urinary trypsin inhibitors (UTI) in regional myocardial ischemia/reperfusion (I/R) injury and its underlying mechanisms involving the role of prosurvival kinases such as phosphatidylinositol-3-OH kinases (PI3K)-Akt and extracellular signal-regulated kinases (ERK 1/2) and apoptotic kinases such as p38 and JNK. Methods: The rats were anesthetized and subjected to an I/R insult consisting of 30-min left anterior descending coronary artery (LAD) occlusion followed by reperfusion. Infarct size was measured after 120 min of reperfusion. UTI was given alone or along with wortmannin (inhibitor of PI3K) or PD098059 (inhibitor of ERK1/2) before LAD occlusion. The phosphorylation of Akt, ERK1/2, p38 and JNK was determined by immunoblotting after 5 min of reperfusion. UTI was administered 10 min before LAD occlusion, and wortmannin and PD098059 were administered 20 min before LAD occlusion. Results: UTI significantly reduced the infarct size compared with the control. Wortmannin or PD098059 alone did not affect the infarct size, but they abolished the UTI-induced cardioprotective effect. UTI significantly reduced the phosphorylation of p38 and JNK, while it enhanced that of Akt and ERK1/2. Conclusions: UTI has a protective effect against regional myocardial I/R injury through activation of survival kinases PI3K-Akt and ERK1/2 and attenuation of p38 and JNK.

Astragalosides attenuate learning and memory impairment in rats following ischemia-reperfusion injury

“…Therefore we hypothesize that AST may produce a marked effect through growth factors and downstream signaling pathways. The ERK, JNK and Akt signaling pathways may regulate neuronal survival and apoptosis following ischemia, but the majority of studies agree that the levels of p-ERK, p-JNK and p-Akt decrease after 24 h or more following ischemia (14,15), therefore the level of p-ERK, p-JNK and p-Akt was detected 22 h after reperfusion in the present study. The p-ERK levels were enhanced following use of a variety of protective agents, such as BDNF and erythropoietin (16)(17)(18).…”

Synergistic Anti-tumor Effect of KLF4 and Curcumin in Human Gastric Carcinoma Cell Line

“…PI3K and cyclinD1 are crucial proteins in PI3K/ Akt signal pathway regulating cell proliferation and cell cycle (Rusyn et al, 2000;Wang et al, 2001;Kim et al, 2009). JNK known as a stress-activated protein kinase involved in JNK/MAPK signal pathway play important role in regulating cell proliferation (Wang et al, 2001).…”

Ulinastatin promotes T lymphocyte apoptosis in rats with severe acute pancreatitis via mitochondrial pathways

“…As an endogenous protection mechanism, the UTIs can counteract stress and attenuate the effects of stress-related injury. Kim et al (2009) found that the UTI has strong enzyme inhibitory activity, which inactivate multiple enzymes, including leukocyte elastase, hyaluronidase, thiol-enzyme, fibrinolytic enzymes, and the serine protease-like trypsin, α-chymotrypsin. The UTI has antiinflammatory effects and can directly affect the neutrophils and mononuclear macrophages; inhibit neutrophil infiltration; and the release of elastase, inflammatory mediators and mononuclear macrophage inflammatory cytokines like TNF-α, IL-1, and IL-8 (Yang et al, 2011).…”