Role of STAT3 in Ischemic Preconditioning

Hattori, Reiji; Maulik, Nilanjana; Otani, Hajime; Zhu, Li; Cordis, Gerald A.; Engelman, Richard M.; Siddiqui, M.A.Q.; Das, Dipak K.

doi:10.1006/jmcc.2001.1456

Cited by 179 publications

(115 citation statements)

References 15 publications

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“…Our data have also demonstrated that apoptosis occurs via the mitochondrial regulated intrinsic apoptosis pathway and involves changes in the bax/bcl2 ratio [8,9]. It has been shown that STAT3 activates bcl2 expression [20]. This activation would be expected to alter the ratio of proapoptotic bax to antiapoptotic bcl2 and would be expected to decrease apoptosis, as we have shown in our model.…”

Section: Commentsupporting

confidence: 80%

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Cardioplegia and Diazoxide Modulate STAT3 Activation and DNA Binding

Hsieh

Wakiyama

Levitsky

et al. 2007

The Annals of Thoracic Surgery

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Background-Previously, we have shown that magnesium supplemented potassium (DSA) cardioplegia and DSA containing diazoxide (DSA+DZX) significantly decrease apoptosis after ischemia. The mechanism for this enhanced cardioprotection was unknown, but we believed that alterations in signal transducers and activators of transcription (STATs) may play a role. To investigate this hypothesis, we examined the effects of DSA and DSA+DZX cardioplegia on STAT1/3 phosphorylation and DNA binding in the in situ blood perfused pig heart model.

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Section: Commentsupporting

confidence: 80%

“…Previous reports have shown that c-Jun interacts with STAT3 and enhances STAT3 DNA-binding [19][20][21][22][23]. In this report, we attempted to examine whether c-Jun interacts with STAT3 in our model by coimmunoprecipitation with anti-STAT3 antibodies followed by Western blot analysis with anti-c-Jun antibodies.…”

Section: Commentmentioning

confidence: 99%

Cardioplegia and Diazoxide Modulate STAT3 Activation and DNA Binding

Hsieh

Wakiyama

Levitsky

et al. 2007

The Annals of Thoracic Surgery

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“…These processes were inhibited when the JAK2 inhibitor, AG-490, was administered before IPC. Complementing the study of Xuan and coworkers (33), investigations carried out by Hattori and coworkers (13) demonstrated that the early phase of IPC was associated with JAK/STAT activation accompanied by an upregulation of Bcl-2 and a downregulation of Bax. Once again, AG-490 was found to cause JAK/STAT inhibition (13).…”

Section: Discussionmentioning

confidence: 84%

“…Complementing the study of Xuan and coworkers (33), investigations carried out by Hattori and coworkers (13) demonstrated that the early phase of IPC was associated with JAK/STAT activation accompanied by an upregulation of Bcl-2 and a downregulation of Bax. Once again, AG-490 was found to cause JAK/STAT inhibition (13). Subsequently, it was reported that cardioprotection associated with tumor necrosis factor-␣-induced preconditioning, as well as IPC, involves STAT3 activation during the early reperfusion phase (19).…”

Section: Discussionmentioning

confidence: 84%

Leptin-induced cardioprotection involves JAK/STAT signaling that may be linked to the mitochondrial permeability transition pore

Smith

Dixon

Wynne

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

100

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Smith CC, Dixon RA, Wynne AM, Theodorou L, Ong SG, Subrayan S, Davidson SM, Hausenloy DJ, Yellon DM. Leptininduced cardioprotection involves JAK/STAT signaling that may be linked to the mitochondrial permeability transition pore. Am J Physiol Heart Circ Physiol 299: H1265-H1270, 2010. First published July 23, 2010; doi:10.1152/ajpheart.00092.2010.-Leptin-induced protection against myocardial ischemia-reperfusion (I/R) injury involves the activation of the reperfusion injury salvage kinase pathway, incorporating phosphatidylinositol 3-kinase-Akt/protein kinase B and p44/42 MAPK, and the inhibition of the mitochondrial permeability transition pore (MPTP). Recently published data indicate that the JAK/STAT signaling pathway, which mediates the metabolic actions of leptin, also plays a pivotal role in cardioprotection. Consequently, in the present study we considered the possibility that JAK/STAT signaling linked to the MPTP may be involved in modulating the cardioprotective actions of leptin. Employing rat in vitro models (Langendorffperfused hearts and cardiomyocytes) of I/R injury, we investigated the actions of leptin (10 nM), administered at reperfusion, in the presence or absence of the JAK2 inhibitor, AG-490 (5 M). Leptin reduced infarct size significantly (control, 60.05 Ϯ 7.41% vs. leptin treated, 29.9 Ϯ 3.24%, P Ͻ 0.05), protection being abolished by AG-490. Time course studies revealed that leptin caused a 171% (P Ͻ 0.001) increase in STAT3/tyrosine-705 phosphorylation at 2.5 min reperfusion; however, increases were not seen at 5, 10, 15, or 30 min reperfusion. Contrasting with STAT3, Akt/serine-473 phosphorylation was not significantly increased until 15 min into the reperfusion phase (140%, P Ͻ 0.05). AG-490 blocked the leptin-induced rise in STAT3 phosphorylation seen at 2.5 min reperfusion but did not influence Akt/serine-473 phosphorylation at 15 min. Leptin reduced the MPTP opening (P Ͻ 0.001), which was blocked by AG-490. This is the first study to yield evidence that JAK/STAT signaling linked to the MPTP plays a role in leptin-induced cardioprotection. Under the experimental conditions employed, STAT3 phosphorylation appears to have occurred earlier during reperfusion than that of Akt. Further research into the interactions between these two signaling pathways in the setting of I/R injury is, however, required. myocardium; ischemia-reperfusion injury; Janus-activated kinase/signal transducer and activator of transcription signaling

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“…Current knowledge of the cellular signalling pathways that initiate ischemic preconditioning suggests a major role for activation of so-called survival kinases such as the PI3K-Akt cascade (Tong et al 2000) and the JAK-STAT pathway (Hattori et al 2001). Several cellular studies by Majewski et al (2004a, b) have demonstrated that activated Akt results in translocation of HK to the mitochondria.…”

Section: Cardioprotective Interventions and Mitochondrial Bound Hkmentioning

confidence: 99%

Mitochondrial hexokinase and cardioprotection of the intact heart

Zuurbier

Smeele

Eerbeek

2009

J Bioenerg Biomembr

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The interaction of hexokinase with mitochondria has emerged as a powerful mechanism in protecting many cell types against cell death. However, the role of mitochondrial hexokinase (mitoHK) in cardiac ischemia-reperfusion injury has as of yet received little attention. In this review we examine whether increased binding of hexokinase to the mitochondrion is also an integral component of cardioprotective signalling. We discuss observations in cardiac mitochondrial activation that directed us to the hypothesis of hexokinase cellular redistribution with reversible, cardioprotective ischemia, summarize the data showing that many cardioprotective interventions, such as ischemic preconditioning, insulin, morphine and volatile anesthetics, increase mitochondrial hexokinase binding within the intact heart, and discuss similarities between mitochondrial hexokinase association and ischemic preconditioning. Although most data indicate that mitochondrial hexokinase may indeed be an integral part of cardioprotection, a definitive proof for a causal relation between the amount of mitoHK and cardiac ischemia-reperfusion injury in the intact heart is eagerly awaited. When such relationship is indeed observed, the association of hexokinase with mitochondria will offer an opportunity to develop new therapies to combat ischemic cardiac diseases.

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Role of STAT3 in Ischemic Preconditioning

Cited by 179 publications

References 15 publications

Cardioplegia and Diazoxide Modulate STAT3 Activation and DNA Binding

Cardioplegia and Diazoxide Modulate STAT3 Activation and DNA Binding

Leptin-induced cardioprotection involves JAK/STAT signaling that may be linked to the mitochondrial permeability transition pore

Mitochondrial hexokinase and cardioprotection of the intact heart

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