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Mammalian models of longevity are related primarily to caloric restriction and alterations in metabolism. We examined mice in which type 5 adenylyl cyclase (AC5) is knocked out (AC5 KO) and which are resistant to cardiac stress and have increased median lifespan of approximately 30%. AC5 KO mice are protected from reduced bone density and susceptibility to(More)
Cell survival and death play critical roles in tissues composed of post-mitotic cells. Cyclic AMP (cAMP) has been known to exert a distinct effect on cell susceptibility to apoptosis, protecting neuronal cells and deteriorating myocardial cells. These effects are primarily studied using protein kinase A activation. In this study we show the differential(More)
BACKGROUND Caveolae, lipid-rich microdomains of the sarcolemma, localize and enrich cardiac-protective signaling molecules. Caveolin-3 (Cav-3), the dominant isoform in cardiac myocytes, is a determinant of caveolar formation. We hypothesized that cardiac myocyte-specific overexpression of Cav-3 would enhance the formation of caveolae and augment cardiac(More)
Transmembrane isoforms of adenylate cyclases (AC) integrate a wide variety of extracellular signals from neurotransmitters to morphogens and can also regulate cAMP production in response to calcium entry. Based on observations in the barrelless mouse strain, the Adcy1 gene (AC1) was involved in the segregation of binocular retinal inputs. To determine the(More)
Various neurotrophic factors that promote axonal regeneration have been investigated in vivo, but the signals that prompt neurons to send out processes in peripheral nerves after axotomy are not well understood. Previously, we have shown oxidized galectin-1 (GAL-1/Ox) promotes initial axonal growth after axotomy in peripheral nerves. However, the mechanism(More)
Vascular remodeling after mechanoinjury largely depends on the migration of smooth muscle cells, an initial key step to wound healing. However, the role of the second messenger system, in particular, the cAMP signal, in regulating such remodeling remains controversial. Exchange protein activated by cAMP (Epac) has been identified as a new target molecule of(More)
The EP4 prostanoid receptor is one of four receptor subtypes for prostaglandin E2. It belongs to the family of G protein-coupled receptors. It was originally identified, similar to the EP2 receptor as a G(s)α-coupled, adenylyl cyclase-stimulating receptor. EP4 signaling plays a variety of roles through cAMP effectors, i.e., protein kinase A and exchange(More)
Adenylyl cyclase, a major target enzyme of beta-adrenergic receptor signals, is potently and directly inhibited by P-site inhibitors, classic inhibitors of this enzyme, when the enzyme catalytic activity is high. Unlike beta-adrenergic receptor antagonists, this is a non- or uncompetitive inhibition with respect to ATP. We have examined whether we can(More)
Sarcalumenin (SAR), specifically expressed in striated muscle cells, is a Ca2+-binding protein localized in the sarcoplasmic reticulum (SR) of the intracellular Ca2+ store. By generating SAR-deficient mice, we herein examined its physiological role. The mutant mice were apparently normal in growth, health, and reproduction, indicating that SAR is not(More)