Pim-3 protects against cardiomyocyte apoptosis in anoxia/reoxygenation injury via p38-mediated signal pathway

Liú, Dan; He, Ming; Yi, Bo; Guo, Wei; Que, Ailing; Zhang, Jixiang

doi:10.1016/j.biocel.2009.05.021

Cited by 26 publications

(20 citation statements)

References 36 publications

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“…Pim-1 is a crucial component of the signalling machinery that counteracts cardiomyocyte apoptosis during the early phase of post-ischemic healing [15,17,39,40]. This was true in our study where restoration of Pim-1 increased the survival of female diabetic cardiomyocytes.…”

Section: Discussionsupporting

confidence: 68%

Rapid onset of cardiomyopathy in STZ-induced female diabetic mice involves the downregulation of pro-survival Pim-1

Moore

Shindikar

Fomison-Nurse

et al. 2014

Cardiovasc Diabetol

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BackgroundDiabetic women are five times more likely to develop congestive heart failure compared with two fold for men. The underlying mechanism for this gender difference is not known. Here we investigate the molecular mechanisms responsible for this female disadvantage and attempt safeguarding cardiomyocytes viability and function through restoration of pro-survival Pim-1.Methods and ResultsDiabetes was induced by injection of streptozotocin in CD1 mice of both genders. Functional and dimensional parameters measurement using echocardiography revealed diastolic dysfunction in female diabetic mice within 8 weeks after STZ-induced diabetes. This was associated with significant downregulation of pro-survival Pim-1 and upregulation of pro-apoptotic Caspase-3, microRNA-1 and microRNA-208a. Male diabetic mice did not show any significant changes at this time point (P < 0.05 vs. female diabetic). Further, the onset of ventricular remodelling was quicker in female diabetic mice showing marked left ventricular dilation, reduced ejection fraction and poor contractility (P < 0.05 vs. male diabetic at 12 and 16 weeks of STZ-induced diabetes). Molecular analysis of samples from human diabetic hearts confirmed the results of pre-clinical studies, showing marked downregulation of Pim-1 in the female diabetic heart (P < 0.05 vs. male diabetic). Finally, in vitro restoration of Pim-1 reversed the female disadvantage in diabetic cardiomyocytes.ConclusionsWe provide novel insights into the molecular mechanisms behind the rapid onset of cardiomyopathy in female diabetics. These results suggest the requirement for the development of gender-specific treatments for diabetic cardiomyopathy.

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Section: Discussionsupporting

confidence: 68%

Rapid onset of cardiomyopathy in STZ-induced female diabetic mice involves the downregulation of pro-survival Pim-1

Moore

Shindikar

Fomison-Nurse

et al. 2014

Cardiovasc Diabetol

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“…Furthermore, it has been reported that the highly sequence homologous and structurally similar Pim-3 kinase protects against cardiomyocyte apoptosis after anoxia/re-oxygenation in rat neonatal cardiac myocytes. 30 Thus, the results of the present study provide further evidence that Pim-1 kinase might be a promising target to alleviate the detrimental effects of cardiac ischaemia/reperfusion injury.…”

Section: Desflurane-induced Postconditioning and Pim-1supporting

confidence: 61%

Desflurane‐induced and ischaemic postconditioning against myocardial infarction are mediated by Pim‐1 kinase

Stumpner

Smul

Redel

et al. 2012

Acta Anaesthesiol Scand

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Background: Anaesthetic-induced (APOST) and ischaemic postconditioning (IPOST) against myocardial infarction are mediated via phosphatidylinositol-3-kinase/Akt. Pim-1 kinase is acting downstream of Akt and has recently been demonstrated to enhance cardiomyocyte survival. We tested the hypothesis that both APOST and IPOST are mediated by Pim-1 kinase. Methods: Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45-min coronary artery occlusion (CAO) and 3-h reperfusion. Animals received either no intervention, the Pim-1 kinase inhibitor II (10 mg/g intraperitoneally) or its vehicle dimethy sulfoxide (10 ml/g intraperitoneally). Three minutes prior to the end of CAO, 1.0 minimum alveolar concentration desflurane was administered for 18 min alone or in combination with Pim-1 kinase inhibitor II. IPOST was induced by three cycles of each 10-s ischaemia/reperfusion, and animals received either IPOST alone or in combination with Pim-1 kinase inhibitor II. Infarct size was determined with triphenyltetrazolium chloride and area at risk with Evans blue. Protein expression of Pim-1 kinase, Bad, phospho-Bad Ser112 and B-cell

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“…Previous reports have shown that PIM1 overexpression increased ERK1/2 phosphorylation in prostate cancer cells [29], increased p38-MAPK activation by phosphorylation in Basophils [31], and increased activation of JNK in cardiomyocytes by PIM3 [32]. Here, we have compared, for the first time, all PIM family members in regards to the expression of these known MAPK pathway members.…”

Section: Discussionmentioning

confidence: 98%

The PIM family of oncoproteins: Small kinases with huge implications in myeloid leukemogenesis and as therapeutic targets

et al. 2014

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PIM kinases are a family of serine/threonine kinases involved in cell survival and proliferation. There is significant structural similarity between the three PIM kinases (PIM1, PIM2 and PIM3) and few amino acid differences. Although, several studies have specifically monitored the role of PIM1 in tumorigenesis, much less is known about PIM2 and PIM3. Therefore, in this study we have used in vitro cell culture models and in vivo bone marrow infection/transplantation to assess the comparative signaling and oncogenic potential of each of the three PIM kinases. All three PIM kinases were able to protect FL5.12 cells from IL-3 withdrawal induced death. Interestingly, the downstream signaling cascades were indistinguishable between the three kinases. Transplantation of murine bone marrow co-expressing MYC and PIM1, PIM2 or PIM3 caused rapid and uniformly lethal myeloid leukemia. De-induction of MYC 18 days following transplantation significantly increased the survival of mice, even with continual expression of PIM kinases. Alternatively, mice treated at the pre-leukemic stage with a PIM kinase inhibitor increased the lifespan of the mice, even with continual expression of the MYC transgene. These data demonstrate the role of PIM kinases in driving myeloid leukemia, and as candidate molecules for therapy against human malignancies.

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Pim-3 protects against cardiomyocyte apoptosis in anoxia/reoxygenation injury via p38-mediated signal pathway

Cited by 26 publications

References 36 publications

Rapid onset of cardiomyopathy in STZ-induced female diabetic mice involves the downregulation of pro-survival Pim-1

Rapid onset of cardiomyopathy in STZ-induced female diabetic mice involves the downregulation of pro-survival Pim-1

Desflurane‐induced and ischaemic postconditioning against myocardial infarction are mediated by Pim‐1 kinase

The PIM family of oncoproteins: Small kinases with huge implications in myeloid leukemogenesis and as therapeutic targets

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