OBJECTIVE: Our goal was to determine if the MKK6-p38 MAPK pathway regulates cardiac intracellular calcium ([Ca(2+)](i)). We also tested if MKK6 might influence expression of SERCA2, a calcium regulatory molecule involved in relaxation, and the …
Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in delayed prostaglandin biosynthesis. The purpose of this study was to evaluate the role of the MAP kinase kinase 6 (MKK6)-p38 MAPK signaling cascade in the regulation of myocardial COX-2 …
AlphaB-crystallin (alphaBC), a small heat shock protein expressed in high levels in the heart, is phosphorylated on Ser-19, 45, and 59 after stress. However, it is not known whether alphaBC phosphorylation directly affects cell survival. In the …
Expression of constitutively active Ras (V12Ras) in cultured neonatal rat ventricular myocytes or targeted cardiac expression of V12Ras in transgenic mice induces myocardial cell growth and expression of genes that are markers of cardiac hypertrophy …
The recently described transcription factor, ATF6, mediates the expression of proteins that compensate for potentially stressful changes in the endoplasmic reticulum (ER), such as reduced ER calcium. In cardiac myocytes the maintenance of optimal …
Many cell types mount elaborate, compensatory responses to stress that enhance survival; however, the intracellular signals that govern these responses are poorly understood. Cardiotrophin-1 (CT-1), a stress-induced cytokine, belongs to the …
Heart failure is associated with dysregulation of intracellular calcium ([Ca(2+)](i)), reduction in myofibrils, and increased activation of Ras, a regulator of signal-transduction pathways. To evaluate the potential effects of Ras on [Ca(2+)](i), we …
Recent evidence indicates that sphingolipids are produced by the heart during hypoxic stress and by blood platelets during thrombus formation. It is therefore possible that sphingolipids may influence heart cell function by interacting with …
The MAPK kinase MKK6 selectively stimulates p38 MAPK and confers protection against stress-induced apoptosis in cardiac myocytes. However, the events lying downstream of p38 that mediate this protection are unknown. The small heat shock protein, …
In various cell types certain stresses can stimulate p38 mitogen-activated protein kinase (p38 MAPK), leading to the transcriptional activation of genes that contribute to appropriate compensatory responses. In this report the mechanism of …