Limits...
Role of Mitogen-Activated Protein Kinases in Myocardial Ischemia-Reperfusion Injury during Heart Transplantation.

Vassalli G, Milano G, Moccetti T - J Transplant (2012)

Bottom Line: The four best-characterized MAPK subfamilies are the c-Jun NH2-terminal kinase (JNK), extracellular signal- regulated kinase-1/2 (ERK1/2), p38 MAPK, and big MAPK-1 (BMK1/ERK5).Most of our current knowledge regarding MAPK activation and cardioprotection comes from studies of preconditioning and postconditioning in nontransplanted hearts.Small-molecule p38 MAPK inhibitors have been tested clinically in patients with chronic inflammatory diseases, but not in transplanted patients, so far.

View Article: PubMed Central - PubMed

Affiliation: Fondazione CardioCentro Ticino, Via Tesserete, 6900 Lugano, Switzerland.

ABSTRACT
In solid organ transplantation, ischemia/reperfusion (IR) injury during organ procurement, storage and reperfusion is an unavoidable detrimental event for the graft, as it amplifies graft inflammation and rejection. Intracellular mitogen-activated protein kinase (MAPK) signaling pathways regulate inflammation and cell survival during IR injury. The four best-characterized MAPK subfamilies are the c-Jun NH2-terminal kinase (JNK), extracellular signal- regulated kinase-1/2 (ERK1/2), p38 MAPK, and big MAPK-1 (BMK1/ERK5). Here, we review the role of MAPK activation during myocardial IR injury as it occurs during heart transplantation. Most of our current knowledge regarding MAPK activation and cardioprotection comes from studies of preconditioning and postconditioning in nontransplanted hearts. JNK and p38 MAPK activation contributes to myocardial IR injury after prolonged hypothermic storage. p38 MAPK inhibition improves cardiac function after cold storage, rewarming and reperfusion. Small-molecule p38 MAPK inhibitors have been tested clinically in patients with chronic inflammatory diseases, but not in transplanted patients, so far. Organ transplantation offers the opportunity of starting a preconditioning treatment before organ procurement or during cold storage, thus modulating early events in IR injury. Future studies will need to evaluate combined strategies including p38 MAPK and/or JNK inhibition, ERK1/2 activation, pre- or postconditioning protocols, new storage solutions, and gentle reperfusion.

No MeSH data available.


Related in: MedlinePlus

Schematic depicting the activation cascades of the four major MAPK subfamilies and corresponding effects on mitochondrial chromosome c release and apoptosis. ERK1/2 and ERK5/BMK1 have been associated with cell survival, whereas JNK and p38 MAPK have been predominantly associated with apoptosis.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3316985&req=5

fig1: Schematic depicting the activation cascades of the four major MAPK subfamilies and corresponding effects on mitochondrial chromosome c release and apoptosis. ERK1/2 and ERK5/BMK1 have been associated with cell survival, whereas JNK and p38 MAPK have been predominantly associated with apoptosis.

Mentions: The MAPK family includes four major serine/threonine protein kinase subfamilies. Each MAPK subfamily comprises successively acting kinases including an upstream MAPK kinase kinase, a MAPK kinase, and a MAPK (Figure 1) [40]. Distinct isoforms of a MAPK bind molecules with different affinities and can activate distinct signaling pathways. In response to a variety of stress stimuli, MAPKs convey extracellular signals to their intracellular targets, thereby regulating cell survival, function, growth, and differentiation [41]. The best characterized MAPK subfamilies are c-Jun NH2-terminal kinases (JNKs), extracellular signal-regulated kinase-1/2 (ERK1/2, also known as p42/p44 MAPK), p38 MAPKs, and the big MAPK-1 (BMK1/ERK5). The role of each MAPK subfamily in myocardial IR injury is discussed in the next sections.


Role of Mitogen-Activated Protein Kinases in Myocardial Ischemia-Reperfusion Injury during Heart Transplantation.

Vassalli G, Milano G, Moccetti T - J Transplant (2012)

Schematic depicting the activation cascades of the four major MAPK subfamilies and corresponding effects on mitochondrial chromosome c release and apoptosis. ERK1/2 and ERK5/BMK1 have been associated with cell survival, whereas JNK and p38 MAPK have been predominantly associated with apoptosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3316985&req=5

fig1: Schematic depicting the activation cascades of the four major MAPK subfamilies and corresponding effects on mitochondrial chromosome c release and apoptosis. ERK1/2 and ERK5/BMK1 have been associated with cell survival, whereas JNK and p38 MAPK have been predominantly associated with apoptosis.
Mentions: The MAPK family includes four major serine/threonine protein kinase subfamilies. Each MAPK subfamily comprises successively acting kinases including an upstream MAPK kinase kinase, a MAPK kinase, and a MAPK (Figure 1) [40]. Distinct isoforms of a MAPK bind molecules with different affinities and can activate distinct signaling pathways. In response to a variety of stress stimuli, MAPKs convey extracellular signals to their intracellular targets, thereby regulating cell survival, function, growth, and differentiation [41]. The best characterized MAPK subfamilies are c-Jun NH2-terminal kinases (JNKs), extracellular signal-regulated kinase-1/2 (ERK1/2, also known as p42/p44 MAPK), p38 MAPKs, and the big MAPK-1 (BMK1/ERK5). The role of each MAPK subfamily in myocardial IR injury is discussed in the next sections.

Bottom Line: The four best-characterized MAPK subfamilies are the c-Jun NH2-terminal kinase (JNK), extracellular signal- regulated kinase-1/2 (ERK1/2), p38 MAPK, and big MAPK-1 (BMK1/ERK5).Most of our current knowledge regarding MAPK activation and cardioprotection comes from studies of preconditioning and postconditioning in nontransplanted hearts.Small-molecule p38 MAPK inhibitors have been tested clinically in patients with chronic inflammatory diseases, but not in transplanted patients, so far.

View Article: PubMed Central - PubMed

Affiliation: Fondazione CardioCentro Ticino, Via Tesserete, 6900 Lugano, Switzerland.

ABSTRACT
In solid organ transplantation, ischemia/reperfusion (IR) injury during organ procurement, storage and reperfusion is an unavoidable detrimental event for the graft, as it amplifies graft inflammation and rejection. Intracellular mitogen-activated protein kinase (MAPK) signaling pathways regulate inflammation and cell survival during IR injury. The four best-characterized MAPK subfamilies are the c-Jun NH2-terminal kinase (JNK), extracellular signal- regulated kinase-1/2 (ERK1/2), p38 MAPK, and big MAPK-1 (BMK1/ERK5). Here, we review the role of MAPK activation during myocardial IR injury as it occurs during heart transplantation. Most of our current knowledge regarding MAPK activation and cardioprotection comes from studies of preconditioning and postconditioning in nontransplanted hearts. JNK and p38 MAPK activation contributes to myocardial IR injury after prolonged hypothermic storage. p38 MAPK inhibition improves cardiac function after cold storage, rewarming and reperfusion. Small-molecule p38 MAPK inhibitors have been tested clinically in patients with chronic inflammatory diseases, but not in transplanted patients, so far. Organ transplantation offers the opportunity of starting a preconditioning treatment before organ procurement or during cold storage, thus modulating early events in IR injury. Future studies will need to evaluate combined strategies including p38 MAPK and/or JNK inhibition, ERK1/2 activation, pre- or postconditioning protocols, new storage solutions, and gentle reperfusion.

No MeSH data available.


Related in: MedlinePlus