Effect of Angiotensin II lype 2 Receptor Blockade on Activation of Mitogen-Activated Protein Kinases after Ischemia-Reperfusion in Isolated Working Rat Hearts

The study has been designed to characterize protein systems involved in the responses of rat hearts to chronic doxorubicin (DOX) treatment. We investigated the influence of DOX on cardiac function, mitogen-activated protein kinases (MAPKs) and heat stress proteins (HSPs). Doxorubicin was administered to rats by intraperitoneal injections over a period of 6 weeks. In control and DOX-treated hearts exposed to 20 min global ischemia and 40 min reperfusion the recovery of contractile function after ischemia/reperfusion (I/R) was determined. The levels and phosphorylation state of proteins in tissue samples were analyzed using specific antibodies. We found an activation of extracellular signal-regulated kinases (ERKs) in rat hearts exposed to DOX treatment and better recovery of contractile function after I/R. Analysis of HSPs showed that DOX induced up-regulation of the levels of HSP60 and down-regulation of HSP70 levels. The levels and/or specific phosphorylation of other studied proteins (p38-MAPK, HSP27, HSP90) were not influenced by DOX. The results point to the possible role of ERKs and some HSPs in mechanisms underlying the response of rat hearts to chronic DOX treatment.

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Lipid Peroxidation Activates Mitogen-Activated Protein Kinases in Testicular Ischemia-Reperfusion Injury

The Journal of Urology ◽

10.1016/j.juro.2006.06.086 ◽

2006 ◽

Vol 176 (4) ◽

pp. 1666-1672 ◽

Cited By ~ 19

Author(s):

Pietro Antonuccio ◽

Letteria Minutoli ◽

Carmelo Romeo ◽

Piero Antonio Nicòtina ◽

Alessandra Bitto ◽

...

Keyword(s):

Lipid Peroxidation ◽

Reperfusion Injury ◽

Protein Kinases ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Mitogen Activated Protein Kinases ◽

Mitogen Activated Protein ◽

Testicular Ischemia

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Mitogen Activated Protein Kinases in Steatotic and Non-Steatotic Livers Submitted to Ischemia-Reperfusion

International Journal of Molecular Sciences ◽

10.3390/ijms20071785 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1785 ◽

Cited By ~ 7

Author(s):

Jiménez-Castro ◽

Cornide-Petronio ◽

Gracia-Sancho ◽

Casillas-Ramírez ◽

Peralta

Keyword(s):

Risk Factor ◽

Clinical Practice ◽

Protein Kinases ◽

Hepatic Steatosis ◽

Ischemic Preconditioning ◽

Liver Surgery ◽

Clinical Studies ◽

Ischemia Reperfusion ◽

Mitogen Activated Protein Kinases ◽

Mitogen Activated Protein

: We analyzed the participation of mitogen-activated protein kinases (MAPKs), namely p38, JNK and ERK 1/2 in steatotic and non-steatotic livers undergoing ischemia-reperfusion (I-R), an unresolved problem in clinical practice. Hepatic steatosis is a major risk factor in liver surgery because these types of liver tolerate poorly to I-R injury. Also, a further increase in the prevalence of steatosis in liver surgery is to be expected. The possible therapies based on MAPK regulation aimed at reducing hepatic I-R injury will be discussed. Moreover, we reviewed the relevance of MAPK in ischemic preconditioning (PC) and evaluated whether MAPK regulators could mimic its benefits. Clinical studies indicated that this surgical strategy could be appropriate for liver surgery in both steatotic and non-steatotic livers undergoing I-R. The data presented herein suggest that further investigations are required to elucidate more extensively the mechanisms by which these kinases work in hepatic I-R. Also, further researchers based in the development of drugs that regulate MAPKs selectively are required before such approaches can be translated into clinical liver surgery.

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