?- but not ?-adrenergic receptors precondition the ischemic heart by a staurosporine-sensitive, chelerythrine-insensitive mechanism

Rorabaugh, Boyd R.; Ross, Seamus; Gaivin, Robert J.; Papay, Robert S.; McCune, Dan F.; Simpson, Paul C.; Perez, Dianne M.

doi:10.1016/j.cardiores.2004.10.009

Cited by 54 publications

(82 citation statements)

References 40 publications

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“…While CAM-α 1A AR mice also display cardiac hypertrophy as in CAM-α 1B AR mice, α 1A AR activation results in positive adaptation of the heart to protect against ischemic damage through preconditioning via cardiac protective IL-6 and JAK/STAT pathways or by preventing apoptosis due to increased glucose uptake (Rorabaugh et al 2005;Papay et al 2013, Perez, unpublished data). In the current study, the only heart abnormality found in CAM-α 1A AR mice was a case of endocarditis/myocarditis.…”

Section: Discussionmentioning

confidence: 99%

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Long-term α1B-adrenergic receptor activation shortens lifespan, while α1A-adrenergic receptor stimulation prolongs lifespan in association with decreased cancer incidence

Collette

Amoth

et al. 2014

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The α 1 -adrenergic receptor (α 1 AR) subtypes, α 1A AR and α 1B AR, have differential effects in the heart and central nervous system. Long-term stimulation of the α 1A AR subtype prolongs lifespan and provides cardio-and neuro-protective effects. We examined the lifespan of constitutively active mutant (CAM)-α 1B AR mice and the incidence of cancer in mice expressing the CAM form of either the α 1A AR (CAM-α 1A AR mice) or α 1B AR. CAM-α 1B AR mice have a significantly shortened lifespan when compared with wild-type (WT) animals; however, the effect was sex dependent. Female CAM-α 1B AR mice lived significantly shorter lives, while the median lifespan of male CAM-α 1B AR mice was not different when compared with that of WT animals. There was no difference in the incidence of cancer in either sex of CAM-α 1B AR mice. The incidence of cancer was significantly decreased in CAM-α 1A AR mice when compared with that in WT, and no sex-dependent effects were observed. Further study is warranted on cancer incidence after activation of each α 1 AR subtype and the effect of sex on lifespan following activation of the α 1B AR. The implications of a decrease in cancer incidence following long-term α 1A AR stimulation could lead to improved treatments for cancer.

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Section: Discussionmentioning

confidence: 99%

“…The CAM receptor genes were expressed under the endogenous promoters, and the animals have been previously characterized (Zuscik et al 2000;Rorabaugh et al 2005). The longevity part of the study included 235 mice, and the pathology study included 157 mice with some overlap.…”

Section: Animalsmentioning

confidence: 99%

Long-term α1B-adrenergic receptor activation shortens lifespan, while α1A-adrenergic receptor stimulation prolongs lifespan in association with decreased cancer incidence

Collette

Amoth

et al. 2014

AGE

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“…Vatner and colleagues also reported a similar observation that cardiac denervation did not block early phase but did blunt late-phase ischemic preconditioning via ␣ 1 -adrenoceptor signaling (102). In search of effective receptor subtypes, Tsuchida et al showed the direct involvement of ␣ 1b -adrenoceptor in ischemic preconditioning (214), but studies using transgenic mice support cardioprotection by ␣ 1a rather than by ␣ 1b (160). On the other hand, the ␤ 2 -adrenoceptor is reported to confer cardioprotection in ischemic preconditioning (209), whereas preischemic ␤ 1 -activation could be an alternative (193).…”

Section: Factors Underlying the Mechanisms Of Preconditioningmentioning

confidence: 96%

“…For example, sustained transgenic activation of ␣ 1b -adrenoceptor did not elicit cardioprotection (160), whereas temporal blockade during the preconditioning period protected the myocardium (68,214). Also, ␤ 1 -adrenoceptor activation is reported to be beneficial during the preconditioning period but deleterious after reperfusion (193).…”

Section: Factors Underlying the Mechanisms Of Preconditioningmentioning

confidence: 99%

Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures

Shoji

Komuro

Kitakaze

2011

American Journal of Physiology-Heart and Circulatory Physiology

330

270

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Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures. Am J Physiol Heart Circ Physiol 301: H1723-H1741, 2011. First published August 19, 2011; doi:10.1152/ajpheart.00553.2011.-Heart diseases due to myocardial ischemia, such as myocardial infarction or ischemic heart failure, are major causes of death in developed countries, and their number is unfortunately still growing. Preliminary exploration into the pathophysiology of ischemia-reperfusion injury, together with the accumulation of clinical evidence, led to the discovery of ischemic preconditioning, which has been the main hypothesis for over three decades for how ischemia-reperfusion injury can be attenuated. The subcellular pathophysiological mechanism of ischemia-reperfusion injury and preconditioninginduced cardioprotection is not well understood, but extensive research into components, including autacoids, ion channels, receptors, subcellular signaling cascades, and mitochondrial modulators, as well as strategies for modulating these components, has made evolutional progress. Owing to the accumulation of both basic and clinical evidence, the idea of ischemic postconditioning with a cardioprotective potential has been discovered and established, making it possible to apply this knowledge in the clinical setting after ischemia-reperfusion insult. Another a great outcome has been the launch of translational studies that apply basic findings for manipulating ischemia-reperfusion injury into practical clinical treatments against ischemic heart diseases. In this review, we discuss the current findings regarding the fundamental pathophysiological mechanisms of ischemiareperfusion injury, the associated protective mechanisms of ischemic pre-and postconditioning, and the potential seeds for molecular, pharmacological, or mechanical treatments against ischemia-reperfusion injury, as well as subsequent adverse outcomes by modulation of subcellular signaling mechanisms (especially mitochondrial function). We also review emerging translational clinical trials and the subsistent clinical comorbidities that need to be overcome to make these trials applicable in clinical medicine. calcium overload; reactive oxygen species; mitochondria; transition pore; comorbidities; clinical trials WHAT DO WE KNOW ABOUT ischemia-reperfusion injury? Because the morbidity and mortality due to ischemic heart diseases have come to the fore in developed countries and are still increasing, it is critically important, both scientifically and socially, to know how cardioprotection is achieved in ischemic myocardium. In fact, in the clinical setting, the application of coronary thrombolysis or immediate percutaneous coronary intervention for faster recanalization has been shown to dramatically improve the outcomes of patients with acute or chronic myocardial ischemia due to impaired coronary blood supply. This finding is founded on the premise that a shorter period of index ischemia...

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“…2,3 These data also raise the possibility that ␣1A subtype-selective agonist therapy might be cardioprotective, as also suggested by some recent studies with ␣1A-transgenic mice. 31,32 …”

Section: Circulation February 13 2007mentioning

confidence: 99%

An α1A-Adrenergic–Extracellular Signal-Regulated Kinase Survival Signaling Pathway in Cardiac Myocytes

et al. 2007

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Background-In ␣1-AR knockout (␣1ABKO) mice that lacked cardiac myocyte ␣1-adrenergic receptor (␣1-AR) binding, aortic constriction induced apoptosis, dilated cardiomyopathy, and death. However, it was unclear whether these effects were attributable to a lack of cardiac myocyte ␣1-ARs and whether the ␣1A, ␣1B, or both subtypes mediated protection. Therefore, we investigated ␣1A and ␣1B subtype-specific survival signaling in cultured cardiac myocytes to test for a direct protective effect of ␣1-ARs in cardiac myocytes. Methods and Results-We cultured ␣1ABKO myocytes and reconstituted ␣1-AR signaling with adenoviruses expressing ␣1-GFP fusion proteins. Myocyte death was induced by norepinephrine, doxorubicin, or H 2 O 2 and was measured by annexin V/propidium iodide staining. In ␣1ABKO myocytes, all 3 stimuli significantly increased apoptosis and necrosis. Reconstitution of the ␣1A subtype, but not the ␣1B, rescued ␣1ABKO myocytes from cell death induced by each stimulus. To address the mechanism, we examined ␣1-AR activation of extracellular signal-regulated kinase (ERK). In ␣1ABKO hearts, aortic constriction failed to activate ERK, and in ␣1ABKO myocytes, expression of a constitutively active MEK1 rescued ␣1ABKO myocytes from norepinephrine-induced death. In addition, only the ␣1A-AR activated ERK in ␣1ABKO myocytes, and expression of a dominant-negative MEK1 completely blocked ␣1A survival signaling in ␣1ABKO myocytes. Conclusions-Our results demonstrate a direct protective effect of the ␣1A subtype in cardiac myocytes and define an ␣1A-ERK signaling pathway that is required for myocyte survival. Absence of the ␣1A-ERK pathway can explain the failure to activate ERK after aortic constriction in ␣1ABKO mice and can contribute to the development of apoptosis, dilated cardiomyopathy, and death.

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?- but not ?-adrenergic receptors precondition the ischemic heart by a staurosporine-sensitive, chelerythrine-insensitive mechanism

Abstract: These data demonstrate that alpha1A-ARs protect the heart from ischemic injury through a staurosporine-sensitive signaling pathway that is independent of protein kinase C.

Cited by 54 publications

References 40 publications

Long-term α1B-adrenergic receptor activation shortens lifespan, while α1A-adrenergic receptor stimulation prolongs lifespan in association with decreased cancer incidence

Long-term α1B-adrenergic receptor activation shortens lifespan, while α1A-adrenergic receptor stimulation prolongs lifespan in association with decreased cancer incidence

Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures

An α1A-Adrenergic–Extracellular Signal-Regulated Kinase Survival Signaling Pathway in Cardiac Myocytes

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