Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.2 (PDK1)
 2,238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein kinases play important roles in intracellular signalling pathways in probably all cells. In the heart, they are involved in the regulation of ion handling, contractility, fuel metabolism and growth. In this review, we discuss the consequences of activation of protein kinases known to be expressed in the heart. We concentrate principally on the following: cyclic AMP-dependent protein kinase, protein kinase C, mitogen-activated protein kinase, Ca2+/calmodulin-dependent protein kinases and pyruvate dehydrogenase kinase.
Cardiovasc Res 1995 Oct
PMID:Intracellular signalling through protein kinases in the heart. 857 96

The consumption of moderate amounts of cocoa products has been associated with reductions in the incidence of cardiovascular diseases. In animal studies, the flavanol (-)-epicatechin (Epi) yields cardioprotection. The effects may be partly due to its capacity to stimulate endothelial nitric oxide synthase (eNOS). The sustained activation of eNOS, as observed with exercise, can serve as a trigger of muscle angiogenesis via the activation of vascular endothelial growth factor (VEGF)-related events. Experiments were pursued to examine the potential of Epi to stimulate myocardial angiogenesis and determine the effects that its combined use with exercise (Ex) may trigger. Hearts obtained from a previous study were used for this purpose. Animals received 1 mg/kg of Epi or water (vehicle) via oral gavage (twice daily). Epi and/or Ex (by treadmill) was provided for 15 days. Results indicate that Ex or Epi significantly stimulate myocardial angiogenesis by ~30% above control levels. The use of Epi-Ex lead to further significant increases (to ~50%). Effects were associated with increases in protein levels and/or activation of canonical angiogenesis pathway associated events (HIF1a, VEGF, VEGFR2, PI3K, PDK, AKT, eNOS, NO, cGMP, MMP-2/-9, Src-1, and CD31). Thus, the use of Epi may represent a safe and novel means to stimulate myocardial angiogenesis.
J Cardiovasc Pharmacol 2012 Nov
PMID:Stimulatory effects of the flavanol (-)-epicatechin on cardiac angiogenesis: additive effects with exercise. 2283 14

Basilar vascular smooth muscle cells (BASMCs) hyperplasia is a prominent feature of cerebrovascular remodeling and stroke during the development of hypertension. Tanshinone IIA (Tan) has been reported to exhibit a protective effect against the pathological features of hypertension. Previous studies have shown that phosphoinostitide-3 kinase (PI3K)/3'-phosphoinostitide dependent kinase (PDK1)/AKT pathway is involved in the regulation of proliferation of various cell types. Therefore, there may be a crosstalk between Tan antihypertension processes and PI3K/PDK1/AKT proliferative effect in BASMCs. To test this hypothesis, we used a 2-kidney, 2-clip hypertension model to examine the effect of Tan on PI3K/PDK1/AKT pathway by cellular, molecular, and biochemical approaches. Our results revealed that the abundance of PDK1 in plasma was paralleled with an increase in blood pressure and the cross-sectional area of basilar artery in hypertensive rats. Tan decreased blood pressure and hypertension-induced PDK1 phosphorylation but produced no effect on the phosphorylation of PI3K. Moreover, Tan attenuated endothelin 1 induced the activation of PDK1/AKT pathway in rat BASMCs. Tan could inhibit cell cycle transition by regulating the expression of cyclin D1 and p27, in turn, prevent proliferation of BASMCs. Our study provides a novel mechanism by which Tan prevents cerebrovascular cell proliferation during hypertension, and thus Tan may be a potential therapeutic agent for cerebrovascular remodeling and stroke.
J Cardiovasc Pharmacol Ther 2015 Nov
PMID:Tanshinone IIA Prevents Rat Basilar Artery Smooth Muscle Cells Proliferation by Inactivation of PDK1 During the Development of Hypertension. 2573 82

Increasing evidence has confirmed that both long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) exert key roles in the pathogenesis of myocardial infarction (MI). Previous microarray assay results revealed that lncRNA LNC_000898 expression was significantly downregulated in acute MI. However, the specific function of LNC_000898 on MI is still unclear. Our study was aimed to explore the role of LNC_000898 on cardiac MI injury and investigate its underlying mechanism. The male C57BL/6 mouse was used as cardiac MI injury animal models, and neonatal mouse ventricular cardiomyocytes (NMCMs) exposed to hypoxia were used as an in vitro model. Quantitative real-time polymerase chain reaction analysis, Western blot analysis, Tunel immunofluorescence staining assay, and cardiac echocardiography measurement were conducted to detect corresponding indicators. The results indicated that LNC_000898 expression was downregulated in marginal tissue of MI and in NMCMs exposed to hypoxia. Overexpression of LNC_000898 decreased cardiomyocyte apoptosis both in vivo and in vitro. In addition, we elaborated that LNC_000898 exerts its inhibitory effect on apoptosis after MI through the miR-375/PDK1 axis. Through miR-375 overexpression or silencing PDK1, the biological effects of LNC_000898 on hypoxia-induced NMCM injury were partially reversed. These data not only demonstrate that LNC_000898 could protect the heart against MI injury by regulating miR-375/PDK1 but also provide a new understanding to better protection of MI injury through the LNC_000898/miR-375/PDK1 axis.
J Cardiovasc Pharmacol 2020 Jul
PMID:Long Noncoding RNA LNC_000898 Alleviates Cardiomyocyte Apoptosis and Promotes Cardiac Repair After Myocardial Infarction Through Modulating the miR-375/PDK1 Axis. 3239 74