To understand the mechanisms by which ethanol inhibits hepatocyte proliferation, we studied the effects of ethanol on p42/44 mitogen-activated protein kinase (MAPK), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) in normal and regenerating rat liver. Treatment of rat hepatocytes with 100 mM ethanol in vitro for 16 h prolonged the activation of p42/44 MAPK and ...

The intracellular protozoan Toxoplasma gondii triggers rapid MAPK activation in mouse macrophages (Mphi). We used synthetic inhibitors and dominant-negative Mphi mutants to demonstrate that T. gondii triggers IL-12 production in dependence upon p38 MAPK. Chemical inhibition of stress-activated protein kinase/JNK showed that this MAPK was also required for parasite-triggered IL-12 production. Ex...

parkinson's disease (pd) is a chronic neurodegenerative condition which has the second largest incidence rate among all other neurodegenerative disorders barring alzheimer's disease (ad). currently there is no cure and researchers continue to probe the therapeutic prospect in cell cultures and animal models of pd. out of several factors contributing to pd prognosis, the role of p38 mapks (mitog...

The role for phosphorylated p38 mitogen-activated protein kinase [p-p38(MAPK)] in b-amyloid plaque deposition [a hallmark of Alzheimer’s disease (AD) pathology] remains ambiguous. We combined immunohistochemistry and stereological sampling to quantify the distribution of plaques and p-p38(MAPK)-immunoreactive (IR) cells in the sensorimotor cortex of 3-, 6and 10-month-old TgCRND8 mice. The aggre...

Differentiation of PC12 cells by nerve growth factor (NGF) requires the activation of various mitogen-activated protein kinases (MAPKs) including p38 MAPK. Accumulating evidence has suggested cross-talk regulation of NGF-induced responses by G protein-coupled receptors, thus we examined whether NGF utilizes G(i/o) proteins to regulate p38 MAPK in PC12 cells. Induction of p38 MAPK phosphorylatio...

OBJECTIVE The basal activity of p38 MAPK has recently been shown to impair myocardial contractility. This kinase is activated by ischemia and short-term hibernation. We hypothesized that p38 MAPK activation may contribute to the contractile deficit that characterizes low-flow ischemia. METHODS In Langendorff-perfused isolated C57BL/6 mouse hearts, perfusion pressure was reduced from 85 to 15 ...

BACKGROUND There is an urgent need to inhibit endothelin-1 (ET-1) induced chronic inflammatory processes in early stages of lung diseases in order to prevent untreatable irreversible stages often accompanied by lung fibrosis and pulmonary hypertension. Nothing is known about the airway inflammation-inducing and/or maintaining role of ET-1 in human airway smooth muscle cells (HASMCs). OBJECTIV...

Transforming growth factor beta1 (TGF-beta1) is a potent fibrotic factor responsible for the synthesis of extracellular matrix. TGF-beta1 acts through the TGF-beta type I and type II receptors to activate intracellular mediators, such as Smad proteins, the p38 mitogen-activated protein kinase (MAPK), and the extracellular signal-regulated kinase pathway. We expressed the kinase domain of the TG...

We show in rat lung microvessel endothelial cells (RLMVEC) that endocytosis is a critical determinant of activation of mitogen-activated protein kinase (MAPK) and thereby regulates endothelial monolayer integrity. In RLMVEC grown in serum-free medium, we observed that albumin supplementation induced the phosphorylation of p38 MAPK within 30 min, which persisted for up to 2 h. Engagement of the ...

Adenosine is arguably the most potent and widespread presynaptic modulator in the CNS, yet adenosine receptor signal transduction pathways remain unresolved. Here, we demonstrate a novel mechanism in which adenosine A1 receptor stimulation leads to p38 mitogen-activated protein kinase (MAPK) activation and contributes to the inhibition of synaptic transmission. Western blot analysis indicated t...