scholarly journals Sustained activation of p42/p44 mitogen-activated protein kinase during recovery from simulated ischaemia mediates adaptive cytoprotection in cardiomyocytes

2000 ◽  
Vol 350 (3) ◽  
pp. 891 ◽  
Author(s):  
Anu PUNN ◽  
James W. MOCKRIDGE ◽  
Saleha FAROOQUI ◽  
Michael S. MARBER ◽  
Richard J. HEADS
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Adaptive Cytoprotection ◽  
Mitogen Activated Protein ◽  
Sustained Activation

scholarly journals Sustained activation of p42/p44 mitogen-activated protein kinase during recovery from simulated ischaemia mediates adaptive cytoprotection in cardiomyocytes

2000 ◽  
Vol 350 (3) ◽  
pp. 891-899 ◽  
Author(s):  
Anu PUNN ◽  
James W. MOCKRIDGE ◽  
Saleha FAROOQUI ◽  
Michael S. MARBER ◽  
Richard J. HEADS
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
P38 Mapk ◽  
Cell Injury ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Neonatal Rat ◽  
Mitogen Activated Protein ◽  
Phosphoinositide 3 Kinase ◽  
Sustained Activation

Delayed cytoprotection (preconditioning) occurs 24h after sublethal simulated ischaemia and reperfusion (SI/R) in neonatal rat ventricular cardiomyocytes. SI/R was used to investigate the role of activation of mitogen-activated protein kinases (MAPKs), stress-activated protein kinases (SAPKs) and phosphoinositide 3-kinase-dependent protein kinase B (PKB)/Akt in cytoprotection. SI resulted in transient dual (Thr/Tyr) phosphorylation of p42/p44-MAPK and p38-MAPK, weak phosphorylation of p46/p54-SAPK, but no phosphorylation of PKB. ‘Reperfusion’ caused further transient phosphorylation of p38-MAPK, but sustained phosphorylation of p42/p44-MAPK (lasting 4h) and of Ser473 of PKB (lasting 2h). Furthermore, SI/R (24h) induced delayed protection against lethal SI, as determined by an increase in cell viability {bioreduction of MTT [3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide]} and a decrease in cell injury (release of creatine kinase). Both protection and phosphorylation of p42/p44-MAPK were blocked by the MEK-1/2 (MAPK/Erk kinase-1/2) inhibitor PD98059 (50µM) when given during SI/R, but not when given during SI alone. The p38-MAPK inhibitor SB203580 (10µM) blocked the p38-MAPK-dependent phosphorylation of activating transcription factor 2 in vitro, and the phosphoinositide 3-kinase inhibitor wortmannin (100nM) blocked PKB phosphorylation on Ser473. However, neither SB203580 nor wortmannin had any effect on delayed protection. Therefore sustained activation of p42/p44-MAPK during simulated ‘reperfusion’ following sublethal SI mediates preconditioning in cardiomyocytes independently of transient activation of p38-MAPK or sustained activation of PKB.

scholarly journals Sustained Activation of the Mitogen-activated Protein Kinase Pathway

1999 ◽  
Vol 274 (7) ◽  
pp. 4347-4353 ◽  
Author(s):  
Lisa J. McCawley ◽  
Shunan Li ◽  
Elizabeth V. Wattenberg ◽  
Laurie G. Hudson
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Kinase Pathway ◽  
Sustained Activation

Sustained Activation of p38 Mitogen-Activated Protein Kinase Contributes to the Vascular Response to Injury

2002 ◽  
Vol 301 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Haisong Ju ◽  
Sandhya Nerurkar ◽  
Charles F. Sauermelch ◽  
Alan R. Olzinski ◽  
Rosanna Mirabile ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Vascular Response ◽  
Mitogen Activated Protein ◽  
Sustained Activation

Sustained activation of MAPK/ERKs signaling pathway in cystic kidneys from bcl-2 −/− mice

2002 ◽  
Vol 283 (5) ◽  
pp. F1085-F1090 ◽  
Author(s):  
Christine M. Sorenson ◽  
Nader Sheibani
Keyword(s):  
Protein Kinase ◽  
B Cell Lymphoma ◽  
Cyst Formation ◽  
Mitogen Activated Protein Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Cystic Kidneys ◽  
Downstream Signaling ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Sustained Activation

Cell proliferation, survival, and differentiation are carefully orchestrated processes during nephrogenesis that become aberrant during renal cyst formation. Signaling through focal adhesion kinase (FAK) impacts these processes, although its role during nephrogenesis requires further delineation. We previously demonstrated that phosphorylation of FAK and paxillin is not downregulated in cystic kidneys from B cell lymphoma/leukemia-2 (bcl-2) −/− mice. Here we examine whether FAK downstream signaling pathways are affected in these cystic kidneys. Cystic kidneys from bcl-2 −/− mice exhibited sustained phosphorylation of Src and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK, ERK1). However, similar levels of expression were noted for phosphorylated c-Jun NH2-terminal kinase, phosphatidylinositol-3-kinase, and its target protein kinase B/ATP-dependent tyrosine kinase in kidneys from postnatal day 20 bcl-2 +/+ and bcl-2 −/− mice. We also examined expression of the adapter protein Shc, implicated in growth and apoptosis. Expression of p66Shc decreases to low levels in postnatal kidneys, whereas p52/p46Shc was constitutively expressed during nephrogenesis. Shc expression was similar in normal and cystic kidneys. Therefore, sustained activation of MAPK/ERKs through the Src/FAK pathway may contribute to the hyperproliferation observed in cystic kidneys from bcl-2 −/− mice.

Sign in / Sign up

Export Citation Format

Share Document