J S Karliner

..These results also suggest large differences in the mitochondrial and cytosolic compartmentalization of NAD(+) in these cell types...

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..In contrast, fresh preparations exhibit early MnSOD release into the cytosol after I/R that is prevented by IPC and cyclosporin A administration...

..Both endogenous and exogenously applied S1P are effective in preventing cell death induced by inhibition of sphingosine kinase...

..We conclude that this cellular model, which is relatively simple to prepare, can be used for in-vitro examination of cardiac protection induced by preconditioning agents, various transgenes, and potentially by targeted gene deletions...

..In contrast, extracellular S1P induces equivalent cardioprotection through PKC epsilon-independent signaling pathways...

..Because protein kinase C (PKC)epsilon activation is necessary for myocardial ischemic preconditioning (IPC) and PKC activators increase SK activity, we tested the hypothesis that SK may be a central mediator of IPC...

..Thus, delivery of LPA to RCMs is affinity-coupled to Edg receptors by gelsolin in a PIP2-regulated process...

..However, there are no data regarding either regulation of beta-adrenergic receptors, particularly at the mRNA level, or adenylylcyclase activity in isolated cardiac myocytes exposed to chronic hypoxia...

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..We sought to determine whether angiotensin II (Ang II) promotes hypertrophy of cardiac directly or via paracrine mechanisms mediated by cardiac fibroblasts...

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..SphK is involved in ischemic preconditioning (IPC). To date no studies in genetically altered animals have examined the role of SphK1 in myocardial ischemia/reperfusion (IR) injury and IPC...

..DMS activates SphK in the cytosol via a PKCepsilon dependent mechanism. The PKCepsilon-SphK-S1P-Akt pathway is involved in the cardiac protection induced by DMS...

..Thus, exogenous S1P induces rapid and reversible S1P1-mediated ERK phosphorylation. S1P-induced adult mouse cardiomyocyte survival requires ERK activation mediated via an S1P1-Gi pathway...

..The utility of the assay is demonstrated by using it to conduct a complete bisubstrate kinetic analysis of rat heart SKase...

..Combination therapy further reduces infarct size. PQQ is superior to metoprolol in protecting mitochondria from ischemia/reperfusion oxidative damage...

..SK2 from rat liver and spleen was also not inhibited by DMS. L-Sphingosine and to a lesser extent dihydrosphingosine and phytosphingosine were effective inhibitors of both forms...

..We conclude that MMP-2 functions not only as a proteolytic enzyme but also as a previously unrecognized active negative regulator of mitochondrial function during superimposed oxidative stress...

..If not, the substitution of agents such as the monosialoganglioside GM-1, which activates sphingosine kinase, or the development of alternative ligands for S1P receptors will be necessary...

..We conclude that signaling pathways involving PKC-epsilon are critical for sustained EtOH-mediated cardioprotection and that Akt may be a downstream effector of resistance to myocardial reperfusion injury...

..Abrupt alternation of anoxic and normoxic perfusion allows cycling between the two states of the enzyme. The possible role in the physiological regulation of complex I activity is discussed...

..These studies reveal that S1P is an important mediator of both IPC and IPOST that is released along with adenosine during each cycle of IPC or IPOST...

..These observations have considerable relevance for future therapeutic approaches to acute and chronic myocardial injury...

..Ischaemic postconditioning combined with sphingosine and S1P rescues the heart from prolonged ischaemia. These observations may have considerable relevance for future therapeutic approaches to acute and chronic myocardial injury...

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..Sphingosine kinase (SKase) has been implicated in the protection of hearts from ischemia/reperfusion injury. This hypothesis was further examined...

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..In isolated mouse hearts, addition of the inhibitor results in a substantial reduction of myocardial infarct size caused by global ischemia/reperfusion injury...

..Ischaemic postconditioning (POST) has been shown to protect hearts against ischaemia/reperfusion injury (IR). To date, no studies have examined the role of SphK1 in POST...

..We conclude that PQQ, which appears to act as a free radical scavenger in ischemic myocardium, is a highly effective cardioprotective agent...

..In addition, these studies show that complex II is fully active in the mitochondrion and not inhibited by OAA regardless of the oxygen concentration...

..Vincristine also exhibited greater protection than the antioxidant MPG. These novel findings may have clinical implications for the prevention of doxorubicin cardiomyopathy...

..The data indicate that detrimental changes are accumulating during protracted ischemia but for up to 90min this damage is not irreversible and hearts can still recover with proper treatment...

..SEW2871 binds to and activates the S1P(1) receptor and initiates a survival signaling pathway similar to that of S1P...

..We conclude that VCR protects cardiomyocytes from MNNG toxicity by regulating PARP-1 activation, intracellular energy metabolism, and prosurvival signaling...

..Biochemical requisites for recovery of down-regulated S1P1 Rs thus differ from those for S1P induction of down-regulation...

..We hypothesize that these benefits can be best understood first at the level of key intracellular signaling cascades in the host myocardium, which can be responsible for functional and structural preservation of the heart...

..These observations highlight the importance of S1P(1) receptors on ventricular myocytes as mediators of inducible resistance against cellular injury during severe hypoxic stress...

..The present study was undertaken to see if aspirin (ASA) antagonised the beneficial effects of captopril or losartan...

..As vincristine and doxorubicin are often used in conjunction to treat patients, it is possible that vincristine could be used to modify the cardiotoxicity of doxorubicin...

..We conclude that activation of endogenous SphK-1 serves a dual regulatory function: it is required for optimal cardiac fibroblast proliferation but is a negative modulator of proinflammatory responses during hypoxia...

..When the cardiomyocyte is reoxygenated after hypoxia, there is a rapid increase in antioxidants, pro-inflammatory cytokines, and stress proteins...

..However, for hearts from females, preconditioning depends on age. Moreover, consistent with previous studies, hearts from females have greater inherent resistance to ischemic injury, possibly involving increased signaling via p-Akt...

..This report is the first demonstration that defined members of the Fos and Jun transcription-factor families specifically regulate this gene under conditions relevant to critical pathophysiological processes...

..5 +/- 1.5 vs. MMP 4.7 +/- 2.0; P = 0.016). Expression of active MMP-2 is sufficient to induce severe ventricular remodeling and systolic dysfunction in the absence of superimposed injury...

..Emphasis is placed on new mechanisms of action that regulate HIF-1alpha, HSF, and heat shock proteins as key responses to hypoxia and ischemia, and possible approaches to therapy based on these data are discussed...

..To directly assess the role of MMP-2 in the absence of superimposed injury, we generated cardiac-specific, constitutively active MMP-2 transgenic mice...

..Our results provide direct evidence that PQQ reduces oxidative stress, mitochondrial dysfunction, and cell death in isolated adult rat cardiomyocytes. These findings provide new insight into the mechanisms of PQQ action in the heart...

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..These studies reveal that SHS promotes tumor angiogenesis and growth. These effects of SHS are associated with increases in plasma VEGF and MCP-1 levels, and EPC, mediated in part by isoprenylation and nicotinic acetylcholine receptors...

..In myxomatous valves, interstitial cells express extracellular matrix-degrading enzymes and it has been postulated that matrix metalloproteinases (MMPs) contribute to these changes...

..Furthermore, investigations of cardioprotection using the Tet system may be aberrantly influenced by sustained preconditioning induced by cardiac transgenesis with tTA...

..Possible models to explain the different titration patterns for the forward and reverse reactions are briefly discussed...

..Epinephrine (EPI) is an important neurotransmitter and hormone. Its role in regulating cardiovascular function at rest and with stress is unclear, however...