Ischemic preconditioning triggers the activation of MAP kinases and MAPKAP kinase 2 in rat hearts

Maulik, Nilanjana; Watanabe, Masahiro; Zu, You Li; Huang, Chi Kuang; Cordis, Gerald A.; Schley, James A.; Das, Dipak K.

doi:10.1016/0014-5793(96)01109-x

Cited by 234 publications

(123 citation statements)

References 27 publications

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“…The pattern of basal total p38 MAPK distribution in control MK2 +/+ mouse ventricular sections was similar to previous report in rat heart (Maulik et al 1996). In addition to the depression of total p38 in MK2 −/− , p38 distribution was altered compared to MK2 +/+ .…”

Section: Effect Of Mapkapk-2 Deficiency On P38 Mapk Cellular Distribusupporting

confidence: 89%

“…In intact heart preparations, total p38 MAPK was detected in the cytosolic, nuclear, and mitochondrial compartments (Maulik et al 1996;Ballard-Croft et al 2005). However, reports on possible cellular translocation of activated p38 MAPK upon ischemic insult are limited and controversial.…”

Section: Introductionmentioning

confidence: 98%

“…However, reports on possible cellular translocation of activated p38 MAPK upon ischemic insult are limited and controversial. For example, Maulik et al (1996) reported p38 translocation to the nucleus and myofibrillar striations. On the other hand, Fryer et al (2001) showed no change.…”

Section: Introductionmentioning

confidence: 99%

“…Total p38 MAPK cellular distribution and expression levels are thought to be modulated by its own downstream highly expressed substrate MAPK-activated protein kinase-2 (MAPKAPK2 or MK2; Zu et al 1997). Activated p38 MAPK phosphorylates nuclear MK2 and forms a complex whereby an MK2 nuclear export signal is unmasked, resulting in its rapid export from the nucleus (Maulik et al 1996;Engel et al 1995;Ben Levy et al 1998). In the cytoplasm, MK2 phosphorylates the small heat shock proteins (HSP) 25/27 (Stokoe et al 1992;Freshney et al 1994;Rouse et al 1994) and αB-crystallin (Hoover et al 2000;Ito et al 2001;Kato et al 1998).…”

Section: Introductionmentioning

confidence: 99%

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MAPKAPK-2 modulates p38-MAPK localization and small heat shock protein phosphorylation but does not mediate the injury associated with p38-MAPK activation during myocardial ischemia

Gorog¹,

Jabr²,

Tanno³

et al. 2009

Cell Stress and Chaperones

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MAPKAPK-2 (MK2) is a protein kinase activated downstream of p38-MAPK which phosphorylates the small heat shock proteins HSP27 and αB crystallin and modulates p38-MAPK cellular distribution. p38-MAPK activation is thought to contribute to myocardial ischemic injury; therefore, we investigated MK2 effects on ischemic injury and p38 cellular localization using MK2-deficient mice (KO). Immunoblotting of extracts from Langendorffperfused hearts subjected to aerobic perfusion or global ischemia or reperfusion showed that the total and phosphorylated p38 levels were significantly lower in MK2 −/− compared to MK2 +/+ hearts at baseline, but the ratio of phosphorylated/total p38 was similar. These results were confirmed by cellular fractionation and immunoblotting for both cytosolic and nuclear compartments. Furthermore, HSP27 and αB crsytallin phosphorylation were reduced to baseline in MK2 −/− hearts. On semiquantitative immunofluorescence laser confocal microscopy of hearts during aerobic perfusion, the mean total p38 fluorescence was significantly higher in the nuclear compared to extranuclear (cytoplasmic, sarcomeric, and sarcolemmal compartments) in MK2 +/+ hearts. However, although the increase in phosphorylated p38 fluorescence intensity in all compartments following ischemia in MK2 +/+ hearts was lost in MK2 −/− hearts, it was basally elevated in nuclei of MK2 −/− hearts and was similar to that seen during ischemia in MK2 +/+ hearts. Despite these differences, similar infarct volumes were recorded in wild-type MK2 +/+ and MK2 −/− hearts, which were decreased by the p38 inhibitor SB203580 (1 μM) in both genotypes. In conclusion, p38 MAPKinduced myocardial ischemic injury is not modulated by MK2. However, the absence of MK2 perturbs the cellular distribution of p38. The preserved nuclear distribution of active p38 MAPK in MK2 −/− hearts and the conserved

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Section: Effect Of Mapkapk-2 Deficiency On P38 Mapk Cellular Distribusupporting

confidence: 89%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

MAPKAPK-2 modulates p38-MAPK localization and small heat shock protein phosphorylation but does not mediate the injury associated with p38-MAPK activation during myocardial ischemia

Gorog¹,

Jabr²,

Tanno³

et al. 2009

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…10 Activation of this pathway is cardioprotective and overexpression of Hsp27 confers protection against ischemia in myocytes. 11 To determine if this pathway is present in human infants and activated by adaptation to chronic hypoxia, we probed normoxic and hypoxic hearts for changes in MAPKAPK-2 and Hsp27.…”

Section: Patient Characteristicsmentioning

confidence: 99%

Activation of Protein Kinases in Chronically Hypoxic Infant Human and Rabbit Hearts

et al. 2002

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Background-Many infants who undergo heart surgery have a congenital cyanotic defect in which the heart is chronically perfused with hypoxic blood. However, the signaling pathways by which infant hearts adapt to chronic hypoxia and resist subsequent surgical ischemia is unknown. Method and Results-We determined the activation and translocation of protein kinase C (PKC) isoforms and mitogen activated protein kinases (MAP kinases) in 15 infants with cyanotic (SaO 2 Ͻ85%) or acyanotic (SaO 2 Ͼ95%) heart defects undergoing surgical repair and in 80 rabbits raised from birth in a hypoxic (SaO 2 Ͻ85%) or normoxic (SaO 2 Ͼ95%) environment. Tissues from infant human and rabbit hearts were processed for Western and in vitro kinase analysis. In human infants with cyanotic heart defects, PKC⑀, p38 MAP kinase, and JUN kinase but not p42/44 MAP kinase were activated and translocated from the cytosolic to the particulate fraction compared with acyanotic heart defects. In rabbit infants there was a parallel response for PKC⑀, p38 MAP kinase, and JUN kinase similar to humans. In infant rabbit hearts inhibition of PKC⑀ with chelerythrine, p38 MAP kinase, with SB203580 and JUN kinase with curcumin abolished the cardioprotective effects of chronic hypoxia but had no effects on normoxic hearts. Conclusions-Infant human and rabbit hearts adapt to chronic hypoxia through activation of PKC⑀, p38 MAP kinase, and JUN kinase signal transduction pathways. These pathways may be responsible for cardioprotection in the chronically hypoxic infant rabbit heart. (Circulation. 2002;106:239-245.)

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Identification of mitogen-activated protein kinase-activated protein kinase-2 as a vimentin kinase activated by okadaic acid in 9L rat brain tumor cells

Cheng

Lai

1998

J. Cell. Biochem.

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Organization of intermediate filament, a major component of cytoskeleton, is regulated by protein phosphorylation/dephosphorylation, which is a dynamic process governed by a balance between the activities of involved protein kinases and phosphatases. Blocking dephosphorylation by protein phosphatase inhibitors such as okadaic acid (OA) leads to an apparent activation of protein kinase(s) and to genuine activation of phosphatase-regulated protein kinase(s). Treatment of 9L rat brain tumor cells with OA results in a drastically increased phosphorylation of vimentin, an intermediate filament protein. In-gel renaturing assays and in vitro kinase assays using vimentin as the exogenous substrate indicate that certain protein kinase(s) is activated in OA-treated cells. With specific protein kinase inhibitors, we show the possible involvement of the cdc2 kinase- and p38 mitogen-activated protein kinase (p38MAPK)-mediated pathways in this process. Subsequent in vitro assays demonstrate that vimentin may serve as an excellent substrate for MAPK-activated protein kinase-2 (MAPKAPK-2), the downstream effector of p38MAPK, and that MAPKAPK-2 is activated with OA treatment. Comparative analysis of tryptic phosphopeptide maps also indicates that corresponding phosphopeptides emerged in vimentin from OA-treated cells and were phosphorylated by MAPKAPK-2. Taken together, the results clearly demonstrate that MAPKAPK-2 may function as a vimentin kinase in vitro and in vivo. These findings shed new light on the possible involvement of the p38MAPK signaling cascade, via MAPKAPK-2, in the maintenance of integrity and possible physiological regulation of intermediate filaments.

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Ischemic preconditioning triggers the activation of MAP kinases and MAPKAP kinase 2 in rat hearts

Cited by 234 publications

References 27 publications

MAPKAPK-2 modulates p38-MAPK localization and small heat shock protein phosphorylation but does not mediate the injury associated with p38-MAPK activation during myocardial ischemia

MAPKAPK-2 modulates p38-MAPK localization and small heat shock protein phosphorylation but does not mediate the injury associated with p38-MAPK activation during myocardial ischemia

Activation of Protein Kinases in Chronically Hypoxic Infant Human and Rabbit Hearts

Identification of mitogen-activated protein kinase-activated protein kinase-2 as a vimentin kinase activated by okadaic acid in 9L rat brain tumor cells

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