Ischemic but Not Pharmacological Preconditioning Requires Protein Synthesis

Matsuyama, Nanritsu; Leavens, John E.; McKinnon, David; Gaudette, Glenn R.; Aksehirli, Tunc O.; Krukenkamp, Irvin B.

doi:10.1161/01.cir.102.suppl_3.iii-312

Cited by 30 publications

(23 citation statements)

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“…However, expression of mRNA encoding the A 2A AR in rat ventricular myocytes (303), together with A 2A AR agonist-me-diated changes in cAMP and contraction of chick (172) and rat myocytes (56, 239,303), support the expression of A 2A ARs on myocytes. This indirect evidence of myocardial expression is supported by a single report of immunological evidence of a canine A 2A AR-like protein in human and porcine ventricular tissue (199).…”

Section: Adenosine Receptor-mediated Cardioprotection: Which Subtypesmentioning

confidence: 57%

“…However, acute changes in gene expression occur during ischemia-reperfusion (120,183) and with protective stimuli (46, 51, 198), and there is support for roles for de novo protein synthesis and/or gene transcription in acute protection with preconditioning (199,241,268). Several studies provide intriguing, if not compelling, support for a transcriptional component in acute adenosinergic protection (120,266).…”

Section: Are Acute Effects Of Adenosine Receptor Activation Entirely mentioning

confidence: 99%

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Acute adenosinergic cardioprotection in ischemic-reperfused hearts

Headrick

Hack

Ashton

2003

American Journal of Physiology-Heart and Circulatory Physiology

150

164

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. Acute adenosinergic cardioprotection in ischemic-reperfused hearts. Am J Physiol Heart Circ Physiol 285: H1797-H1818, 2003; 10.1152/ajpheart.00407. 2003.-Cells of the cardiovascular system generate and release purine nucleoside adenosine in increasing quantities when constituent cells are "stressed" or subjected to injurious stimuli. This increased adenosine can interact with surface receptors in myocardial, vascular, fibroblast, and inflammatory cells to modulate cellular function and phenotype. Additionally, adenosine is rapidly reincorporated back into 5Ј-AMP to maintain the adenine nucleotide pool. Via these receptor-dependent and independent (metabolic) paths, adenosine can substantially modify the acute response to ischemic insult, in addition to generating a more sustained ischemia-tolerant phenotype (preconditioning). However, the molecular basis for acute adenosinergic cardioprotection remains incompletely understood and may well differ from more widely studied preconditioning. Here we review current knowledge and some controversies regarding acute cardioprotection via adenosine and adenosine receptor activation.adenosine; adenosine receptor activation; ischemia; reperfusion injury THE HEART possesses its own intrinsic protective responses, including the adenosine receptor system, which enhance resistance to ischemic insult. An understanding of the mechanisms involved in these responses not only informs us of how the heart reacts to injurious stimuli, but may provide avenues for developing novel protective strategies applicable in the setting of ischemia-reperfusion. The purine nucleoside adenosine was attributed with cardioregulatory functions almost 75 years ago (64), and since then has emerged as a crucially important control substance in essentially every tissue of the body. In the heart adenosine not only plays a role in regulating growth and differentiation, angiogenesis, coronary blood flow, cardiac conduction and heart rate, substrate metabolism, and sensitivity to adrenergic stimulation (23,67,68,73,74,260,271,283), but may play a role as an endogenous determinant of ischemic tolerance (189,225,245,259,311,312,318). From a therapeutic viewpoint, adenosine-based therapies protect against ischemic injury in a variety of animal models (72,177,208,265,288) and in human cardiac tissue (34, 36, 37,240,296). However, much remains unclear regarding the roles and mechanisms of action of adenosine in producing acute protection against ischemia and reperfusion. Generation of Endogenous Adenosine During InsultEndogenous adenosine levels increase rapidly with ischemic insult (104,109,285,286) to mediate a retaliatory response. This protective pool of adenosine can be formed via dephosphorylation of 5Ј-AMP by intra-and extracellular 5Ј-nucleotidases and from S-adenosylhomocysteine (SAH) via SAH hydrolase. Extracellular adenosine is rapidly taken into cells via a facilitative transporter (131). Within cells it is either deaminated by adenosine deaminase or rephosphorylated to 5Ј-AMP via adenosine kinase. O...

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Section: Adenosine Receptor-mediated Cardioprotection: Which Subtypesmentioning

confidence: 57%

Section: Are Acute Effects Of Adenosine Receptor Activation Entirely mentioning

confidence: 99%

Acute adenosinergic cardioprotection in ischemic-reperfused hearts

Headrick

Hack

Ashton

2003

American Journal of Physiology-Heart and Circulatory Physiology

150

164

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“…S7) (55)(56)(57). The protective potential of redox-signaling can be seen in the cytoprotective effects associated with low fluxes of ROS or SNO prior to subsequent ischemic insults, including the preservation of protein synthesis (58,59). Protein synthesis can be inhibited by oxidative damage in part by modification of elongation factor 2 (EF2) (60).…”

Section: Discussionmentioning

confidence: 99%

Identification and Quantification of S-Nitrosylation by Cysteine Reactive Tandem Mass Tag Switch Assay

Murray¹,

Uhrigshardt²,

O’Meally

et al. 2012

Molecular & Cellular Proteomics

166

176

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Redox-switches are critical cysteine thiols that are modified in response to changes in the cell's environment conferring a functional effect. S-nitrosylation (SNO) is emerging as an important modulator of these regulatory switches; however, much remains unknown about the nature of these specific cysteine residues and how oxidative signals are interpreted. Because of their labile nature, SNO-modifications are routinely detected using the biotin switch assay. Here, a new isotope coded cysteine thiolreactive multiplex reagent, cysTMT 6 , is used in place of biotin, for the specific detection of SNO-modifications and determination of individual protein thiol-reactivity. S-nitrosylation was measured in human pulmonary arterial endothelia cells in vitro and in vivo using the cysTMT 6 quantitative switch assay coupled with mass spectrometry. Cell lysates were treated with S-nitrosoglutathione and used to identify 220 SNO-modified cysteines on 179 proteins. Using this approach it was possible to discriminate potential artifacts including instances of reduced protein disulfide bonds (6) and S-glutathionylation (5) as well as diminished ambiguity in site assignment. Quantitative analysis over a range of NO-donor concentrations (2, 10, 20 M; GSNO) revealed a continuum of reactivity to SNO-modification. Cysteine response was validated in living cells, demonstrating a greater number of less sensitive cysteine residues are modified with increasing oxidative stimuli. Of note, the majority of available cysteines were found to be unmodified in the current treatment suggesting significant additional capacity for oxidative modifications. These results indicate a possible mechanism for the cell to gauge the magnitude of oxidative stimuli through the progressive and specific accumulation of modified redox-switches. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.013441, 1-12, 2012.Changes in the oxidative balance can affect many aspects of cellular physiology through redox-signaling (1, 2). Oxidative species modify critical cysteine thiols, known as redoxswitches, which sense and respond to the cell's fluctuating environment (3, 4). Depending on the magnitude, these fluctuations can affect normal metabolic processes, activate protective mechanisms or be cytotoxic. Redox-signaling is thought to derive from the integration of the type and concentration of oxidizing species, their associated chemical biology and cellular localization (5-7). However, less is known about the nature of the cysteine residues targeted or how oxidative signals are interpreted within the cell.S-nitrosylation (SNO), 1 also known as S-nitrosation, is emerging as an important regulatory post-translational modification in many cellular processes (8). This modification is the result of the covalent addition of an NO group to a cysteine thiol; however, the specific mechanism of this addition has not been fully determined (9). SNO possesses the essential criteria for a signaling modification including a rapid reaction, specificity and enzymatic reduction (10)....

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“…Changes in protein synthesis during 30 min isoflurane exposure and 15 min memory period would be of limited significance. Indeed, cardioprotection by pharmacological preconditioning is not blocked by inhibition of protein synthesis (19). In addition, APC, like other preconditioning stimuli, is well known to induce various signaling kinases that also target mitochondria.…”

Section: Discussionmentioning

confidence: 99%