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In conclusion, our data indicated that PDK4 potentially contributes to the hepatic steatosis in NASH via regulating several signaling pathway and PDK4 may be a new therapeutic strategy against NAFLD.
our results suggest that PDK2/4 can be a potential target for the development of pharmacotherapy for the treatment of acute inflammatory pain
Taken together these data support a model where PDHK4 regulates KRAS signalling and its tumorigenic properties and suggest that inhibition of PDHK4 could represent a novel therapeutic strategy to target KRAS mutant colorectal and lung cancers
PDK4 mediates cisplatin-induced acute kidney injury.
Pyruvate dehydrogenase kinase 4 is a direct transcriptional target of FoxO1 in the heart. FoxO1 directly regulates Pdk4 transcription in the heart, thereby controlling PDH activity and subsequent glucose oxidation rates.
inhibition of PDK4 activity in Hepatocellular carcinoma cells increased cyclin E1, cyclin A2, and E2F1 proteins.
FXR may promote the proliferation of tumor cells and the hepatocytes in the process of liver regeneration by activating the PDK4-mediated metabolic reprogramming to generate glycolytic intermediates essential for rapid biomass generation, establishing a mechanistic link between cell proliferation and metabolic switch.
Taken together, our results suggest that LPS induces PDK4 expression and alters glucose metabolism via the JNK pathway.
upregulation of PDK4 promotes vascular calcification by increasing osteogenic markers with no adverse effect on bone formation, demonstrating that PDK4 is a therapeutic target for vascular calcification.
PDK2/4 induction and the subsequent lactate surge induce the metabolic shift in the diabetic dorsal root ganglion thereby contributing to the pathogenesis of painful diabetic neuropathy.
These findings reveal that there are divergent roles of PDKs during oocyte maturation and indicate a new mechanism controlling meiotic structure.
Double-knockout mice with global deletion of PDK2 and PDK4, which results in constitutively activated pyruvate dehydrogenase, preferentially oxidize glucose in muscle.
PDK4 promotes tumorigenesis through activation of the CREB-RHEB-mTORC1 signaling cascade.
Diminished insulin signaling evident at 1 wk on the high fat diet did not occur in pyruvate dehydrogenase kinase 4 knockout mice.
The Pdk4 gene knockdown led to better glucose tolerance than the Pdk2 gene knockdown. Hepatic Pdk4 may be critically involved in the pathogenesis of diabetes.
These results suggest a role for PDK4 in regulating the PDH complex in muscle and promoting gluconeogenic precursor recirculation during recovery from exhaustive exercise.
loss of both Pdk2 and Pdk4 attenuated HSC quiescence, glycolysis, and transplantation capacity.
Deletion of PDK4 prevented Angiotensin II-induced diastolic dysfunction and normalized glucose oxidation to basal levels.
the role of IL-6 signalling in adipose tissue during exercise
Data suggest that up-regulation of cardiac PDK4 by high-fat diet (HFD) occurs in conjunction with time-dependent activation of E2F1 transcription factor (E2F1); HFD may initiate early cardiac metabolic alterations through cyclin D1/E2F1/PDK4 axis.
miR-15b-5p acted as a tumor suppressor in osteosarcoma by directly targeting PDK4 and inhibiting its expression.
Results show that PDK4-specific 5'UTR DNA methylation is positively associated with eicosapentaenoic and arachidonic acid in adult males.
it was found that low expression of FAM210B was significantly correlated with decreased survival and enhanced metastasis in vivo and in vitro, and the loss of FAM210B led to an increased mitochondrial respiratory capacity and reduced glycolysis through the downregulation of pyruvate dehydrogenase kinase 4 (PDK4).
Low PDK4 expression is associated with lung tumorigenesis.
Increased PDK4 expression is associated with colon cancer.
We found that PDK4 gene and protein expression was significantly elevated in pulmonary arterial hypertension pericytes and correlated with reduced mitochondrial metabolism, higher rates of glycolysis, and hyperproliferation
Inhibition of CK2 increased the expression of metabolic regulators, PDK4 and AMPK along with the key cellular energy sensor CREB.
These findings indicate that the TGFbeta/PDK4 signaling axis plays an important role in the response of colorectal cancer to chemotherapy.
Combined speed endurance and endurance exercise amplify the exercise-induced PGC-1alpha and PDK4 mRNA response in trained human muscle.
High PDK4 expression is associated with hepatocellular cancer.
Fatty acids induce the expression of PDK4 mRNA, which was increased in myotubes cultured from obese and T2DM donors.
Swiss PDB Viewer identifies NFkappaB subunit p100/p49 as a potential interacting partner for PDK4. Relationship between PDK4 and apoptosis is suggested.
ZBTB2 may increase cell proliferation by reprogramming glucose metabolic pathways to favor glycolysis by upregulating PDK4 expression via repression of RelA/p65 expression
Methylation increased in PDK4, IL1 B, IL6, and TNF promoters 12 months after gastric bypass.
Data show that the orphan nuclear receptor estrogen related receptor gamma (ERRgamma) plays a critical role in hypoxia-mediated activation of pyruvate dehydrogenase kinase 4 (PDK4) gene expression.
Preoperative carbohydrate supplementation was found to ameliorate postoperative insulin sensitivity by reducing muscle inflammatory responses and improved insulin inhibition of FOXO1-mediated PDK4 mRNA and protein expression after surgery.
Temporal and spatial expression analysis indicated that porcine PDK4 gene is highly expressed in skeletal muscle and the highest in neonatal pigs.
This gene is a member of the PDK/BCKDK protein kinase family and encodes a mitochondrial protein with a histidine kinase domain. This protein is located in the matrix of the mitrochondria and inhibits the pyruvate dehydrogenase complex by phosphorylating one of its subunits, thereby contributing to the regulation of glucose metabolism. Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin.
pyruvate dehydrogenase kinase 4
, pyruvate dehydrogenase kinase, isoenzyme 4
, pyruvate dehydrogenase kinase, isozyme 4
, [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial
, pyruvate dehydrogenase, lipoamide, kinase isozyme 4, mitochondrial
, pyruvate dehydrogenase kinase isozyme 4
, pyruvate dehydrogenate kinase 4