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Prostacyclin (PGI(2)) is one of the important vascular prostanoids, the effects of which counteract those of thromboxane (TXA(2)), and these 2 prostanoids provide an important balance in cardiovascular homeostasis. The clinical experience of COX-2 selective inhibitors having unexpected adverse effects in patients with cardiovascular risk has opened up a(More)
Caveolar localization of protein kinase C and the regulation of caveolar function by protein kinase C are well known. This study was undertaken to examine whether caveolin subtypes interact with various protein kinase C isoenzymes using the caveolin scaffolding domain peptide. When protein kinase C-alpha, -epsilon, and -zeta were overexpressed in COS cells(More)
The changing relationship between stimuli and responses after prolonged receptor stimulation is a general feature of hormonal signaling systems, termed desensitization. This phenomenon has been best exemplified in the covalent modification of the G protein-linked catecholamine receptors. However, other components within this signaling pathway can be(More)
Cyclic AMP production within cells is altered upon protein kinase C (PKC) activation; however, whether PKC directly modulates adenylyl cyclase (AC) catalytic activity has been controversial. Molecular studies have elucidated the existence of multiple PKC isoenzymes although the functional role of this diversity is not clear. Using purified PKC and AC(More)
Abstract Type V adenylyl cyclase (AC) was stably over-expressed in HEK293 cells (293AC-V). Forskolin-stimulated cAMP accumulation in 293AC-V was 5 times as great as that in control cells. PMA, a protein kinase C (PKC) activator, enhanced cAMP accumulation in 293AC-V cells dose-and time-dependently and this enhancement was abolished by staurosporine. Insulin(More)
BACKGROUND The hedgehog (Hh) pathway has been implicated in the pathogenesis of cancer including pancreatic ductal adenocarcinoma (PDAC). Recent studies have suggested that the oncogenic function of Hh in PDAC involves signaling in the stromal cells rather than cell autonomous effects on the tumor cells. However, the origin and nature of the stromal cell(More)
Type 2 diabetes is preceded by the development of insulin resistance, in which the action of insulin is impaired, largely in skeletal muscles. Caveolin-3 (Cav3) is a muscle-specific subtype of caveolin, an example of a scaffolding protein found within membranes. Cav is also known as growth signal inhibitor, although it was recently demonstrated that the(More)
The sympathetic nervous system is designed to respond to stress. Adenylyl cyclase (AC) is the keystone of sympathetic transmission, yet its role in response to acute overload in the heart or in the pathogenesis of heart failure is controversial. We examined the effects of pressure overload, induced by thoracic aortic banding, in mice in which type 5 AC, a(More)
In a genetically engineered mouse line with disruption of type 5 adenylyl cyclase (AC5-/-), a major cardiac isoform, there was no compensatory increase in other isoforms of AC in the heart. Both basal and isoproterenol (ISO)-stimulated AC activities were decreased by 30% to 40% in cardiac membranes. The reduced AC activity did not affect cardiac function(More)
Prostanoids consisting of prostaglandins (PGs) and thromboxanes (TXs) are produced from arachidonic acids, representative fatty acids contained in cell membrane, by the sequential actions of phospholipase A(2), cyclooxygenases and respective prostanoid synthases. Prostanoids are released outside of the cells immediately after biosynthesis and exert a wide(More)