Hemodynamic abnormalities are important in the pathogenesis of the excess mesangial matrix deposition of diabetic and other glomerulopathies. p38-Mitogen-activated protein (MAP) kinase, an important intracellular signaling molecule, is activated in the glomeruli of diabetic rats. We studied, in human mesangial cells, the effect of stretch on p38 MAP kinase activation and the role of p38 MAP kin...

Mitogen-activated protein (MAP) kinases bind tightly to many of their physiologically relevant substrates. We have identified a new subfamily of murine serine/threonine kinases, whose members, MAP kinase-interacting kinase 1 (Mnk1) and Mnk2, bind tightly to the growth factor-regulated MAP kinases, Erk1 and Erk2. MNK1, but not Mnk2, also binds strongly to the stress-activated kinase, p38. MNK1 c...

Objective: This study was aimed at investigating the immunoregulatory effects of trypanosomal lipophosphoglycan (LPG) anchored to trypanosome membranes, including formation neutrophil extracellular traps (NETs) and cytokine release after parasite infection. The interaction cell surface TLR receptors with LPG, which signals cellular responses during Trypanosma brucei infection, systematically in...

Air pollutants including diesel exhaust particles (DEPs) have been shown to enhance allergic responses. DEPs stimulate airway epithelial cells to produce various cytokines; however, the intracellular signal transduction pathway and the involvement of reduction and oxidation (redox) control in DEP-activated signaling have not been determined. In the present study, we therefore examined the role ...

We characterized the tracheal and bronchial relaxation caused by proteinase-activated receptor-2 (PAR-2) activation in ddY mice and/or in wild-type and PAR-2-knockout mice of C57BL/6 background. Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-NH(2)) and Thr-Phe-Leu-Leu-Arg-amide, PAR-2- and PAR-1-activating peptides, respectively, caused relaxation in the isolated ddY mouse trachea and main bronchus. The...

The p38 mitogen-activated protein (MAP) kinases are a family of serine/threonine protein kinases that play important roles in cellular responses to inflammation and external stress. Inhibitors of the p38 MAP kinase have shown promise for potential treatment of inflammatory disorders such as rheumatoid arthritis, acute coronary syndrome, psoriasis, and Crohn's disease. We identified a novel clas...

MYOCARDIAL ADAPTATION TO ISCHEMIA occurs through the activation of several tyrosine kinases (3). Phosphorylation of tyrosine kinases has been shown to be linked with the activation of both phospholipase C and phospholipase D, leading to the activation of multiple kinases including PKC and mitogen-activated protein (MAP) kinases. The MAP kinases play an essential role in mediating intracellular ...

Atherosclerosis is the underlying pathological process of most cardiovascular disease. A critical component of the "response to retention" hypothesis of atherogenesis is proteoglycan/low density lipoprotein (LDL) binding. Transforming growth factor beta (TGF-beta) is present in atherosclerotic lesions, regulates vascular smooth muscle cell (VSMC) proteoglycan synthesis via an unknown signaling ...

The mitogen-activated protein (MAP) kinases contribute to altered cell growth and function in a variety of disease states. However, their role in the endothelial complications of diabetes mellitus remains unclear. Human endothelial cells were exposed for 72 h to 5 mM (control) or 25 mM (high) glucose or 5 mM glucose plus 20 mM mannitol (osmotic control). The roles of p38 and p42/44 MAP kinases ...

Cytoplasmic pH (pH(i)) was evaluated during Na(+)-glucose cotransport in Caco-2 intestinal epithelial cell monolayers. The pH(i) increased by 0.069 +/- 0.002 within 150 s after initiation of Na(+)-glucose cotransport. This increase occurred in parallel with glucose uptake and required expression of the intestinal Na(+)-glucose cotransporter SGLT1. S-3226, a preferential inhibitor of Na(+)/H(+) ...