Ischemic preconditioning triggers tyrosine kinase  signaling: a potential role for MAPKAP kinase 2

Maulik, Nilanjana; Yoshida, Tetsuya; Zu, You Li; Sato, Motoaki; Banerjee, Anirban; Das, Dipak K.

doi:10.1152/ajpheart.1998.275.5.h1857

Cited by 111 publications

(107 citation statements)

References 28 publications

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“…Marked activation of p38 was observed in isolated, perfused rat hearts [72], with several studies showing that p38 activation during ischemia promotes injury [73,74]. Equally, numerous studies have also demonstrated a protective role for p38 during ischemia [75][76][77]. In our cell SIRT1 modulates MAPK pathways model, simulated IR triggered an increase in the phosphop38/total p38 ratio, with Resv treatment reducing p38 phosphorylation to control levels.…”

Section: Discussionmentioning

confidence: 72%

SIRT1 modulates MAPK pathways in ischemic–reperfused cardiomyocytes

Becatti

Taddei

Cecchi

et al. 2012

Cell. Mol. Life Sci.

129

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SIRT1, an ubiquitous NAD(?)-dependent deacetylase that plays a role in biological processes such as longevity and stress response, is significantly activated in response to reactive oxygen species (ROS) production. Resveratrol (Resv), an important activator of SIRT1, has been shown to exert major health benefits in diseases associated with oxidative stress. In ischemia-reperfusion (IR) injury, a major role has been attributed to the mitogenactivated protein kinase (MAPK) pathway, which is upregulated in response to a variety of stress stimuli, including oxidative stress. In neonatal rat ventricular cardiomyocytes subjected to simulated IR, the effect of Resv-induced SIRT1 activation and the relationships with the MAPK pathway were investigated. Resv-induced SIRT1 overexpression protected cardiomyocytes from oxidative injury, mitochondrial dysfunction, and cell death induced by IR. For the first time, we demonstrate that SIRT1 overexpression positively affects the MAPK pathway-via Akt/ASK1 signaling-by reducing p38 and JNK phosphorylation and increasing ERK phosphorylation. These results reveal a new protective mechanism elicited by Resv-induced SIRT1 activation in IR tissues and suggest novel potential therapeutic targets to manage IR-induced cardiac dysfunction.

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Section: Discussionmentioning

confidence: 72%

SIRT1 modulates MAPK pathways in ischemic–reperfused cardiomyocytes

Becatti

Taddei

Cecchi

et al. 2012

Cell. Mol. Life Sci.

129

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“…17,35 In the heart, p38 MAPK activation by preconditioning triggers a kinase cascade involving MAPK-activated protein kinase 2 (MAPKAPK2). 38,39 Heat shock protein HPS27 represents one of the substrates of MAPKAPK2 40 and once phosphorylated HPS27 can bind to actin increasing the resistance of cytoskeleton to stress. 41 A possible role of HPS27 in liver preconditioning is emerging from recent observations showing the association between HPS27 induction and the prevention of hepatic injury after ischemia and reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Signal Pathway Involved in the Development of Hypoxic Preconditioning in Rat Hepatocytes

Carini¹,

Cesaris²,

Splendore³

et al. 2001

Hepatology

102

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Ischemic preconditioning improves liver resistance to hypoxia and reduces reperfusion injury following transplantation. However, the intracellular signals that mediate the development of liver hypoxic preconditioning are largely unknown. We have investigated the signal pathway leading to preconditioning in freshly isolated rat hepatocytes. Hepatocytes were preconditioned by 10-minute incubation under hypoxic conditions followed by 10 minutes of reoxygenation and subsequently exposed to 90 minutes of hypoxia. Preconditioning reduced hepatocyte killing by hypoxia by about 35%. A similar protection was also obtained by preincubation with chloro-adenosine or with A 2A -adenosine receptor agonist CGS21680, whereas A 1 -adenosine receptor agonist N-phenyl-isopropyladenosine (R-PIA) was inactive. Conversely, the development of preconditioning was blocked by A 2 -receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX), but not by A 1 -receptor antagonist 8-cyclopenthyl-1,3-dipropylxanthine (DPCPX). In either preconditioned or CGS21680-treated hepatocytes a selective activation of ␦ and protein kinase C (PKC) isoforms was also evident. Inhibition of heterotrimeric G i protein or of phospholypase C by, respectively, pertussis toxin or U73122, prevented PKC activation as well as the development of preconditioning. MEK inhibitor PD98509 did not interfere with preconditioning that was instead blocked by p38 MAP kinase inhibitor SB203580. The direct activation of p38 MAPK by anisomycin A mimicked the protection against hypoxic injury given by preconditioning. Consistently, an increased phosphorylation of p38 MAPK was observed in preconditioned or CGS21680-treated hepatocytes, and this effect was abolished by PKC-blocker, chelerythrine. We propose that a signal pathway involving A 2A -adenosine receptors, G i -proteins, phospholypase C, ␦-and -PKCs, and p38 MAPK, is responsible for the deve- The term ischemic preconditioning refers to the resistance to ischemic injury acquired by tissue following one or more brief periods of ischemia followed by reperfusion. 1,2 Ischemic preconditioning was first described in the myocardium, 1 but has been shown in several other organs, including the brain, the skeletal muscles, and the small intestine. 3 In the heart, ischemic preconditioning occurs in 2 phases: an early phase (early preconditioning) that immediately follows the transient hypoxia and lasts 2 to 3 hours and a late phase (late preconditioning), which begins 12 to 24 hours from the transient ischemia and lasts for about 3 to 4 days. 3 Recent studies have shown that the same phenomenon could also be observed in the liver. [4][5][6][7][8][9][10] In particular, 10-minute interruption of liver blood supply in anesthetized rats followed by 10 minutes of reperfusion reduces transaminases released during a subsequent 90-minute period of ischemia and 90-minute reoxygenation. 5 A similar effect has also been observed in steatosic livers following heat shock preconditioning. 7 Furthermore, ischemic preconditioning before cold preserva...

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“…The results, however, remain contradictory. Early reports showed that activation of p38 is benefi cial 63,64 , followed by later studies demonstrating the opposite 65,66 . More recent data suggest alternative pathways are at work when p38 is activated, producing divergent eff ects 67 .…”

Section: Role Of P38 In Cardioprotectionmentioning

confidence: 99%

Modulation of Ucp2 Expression by P38 - A Link to Cardioprotection

E¹,

Modrianský²

2008

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background: Discovery of uncoupling protein 2 (UCP2) in 1997 and demonstration of its wide tissue expression has triggered an important question about controlled oxidative phosphorylation uncoupling and the physiological function of this process. Uncoupling protein 2 (UcP2) is a mitochondrial protein that can infl uence the mitochondrial membrane potential and hence the production of reactive oxygen species by mitochondria. It is also thought to be involved in apoptotic signaling pathways and it has been suggested to be important in cardio-and neuroprotection.Methods and results: We examined the recent literature (2003)(2004)(2005)(2006)(2007) in the MedLine database for evidence linking p38, one of the stress-related protein kinases, with modulation of UCP2 expression in the heart. While two reports clearly demonstrate p38 as down-regulating UcP2 expression, only circumstantial evidence exists for cardiomyocytes. Confl icting results on p38-regulated cardiomyocyte survival after ischemia leave an open venue for hypotheses on the diff erential regulation of protein expression, including UCP2.Conclusions: Reviewing the evidence connecting UCP2 and its cytoprotective activities, we propose a tissue specifi c link that may explain the variable infl uence of p38 via modulation of UCP2 expression.

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Ischemic preconditioning triggers tyrosine kinase signaling: a potential role for MAPKAP kinase 2

Cited by 111 publications

References 28 publications

SIRT1 modulates MAPK pathways in ischemic–reperfused cardiomyocytes

SIRT1 modulates MAPK pathways in ischemic–reperfused cardiomyocytes

Signal Pathway Involved in the Development of Hypoxic Preconditioning in Rat Hepatocytes

Modulation of Ucp2 Expression by P38 - A Link to Cardioprotection

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