Androgen regulated protein and pyruvate dehydrogenase kinase 4 in severe erectile dysfunction: A gene expression analysis, and computational study of protein structure

2021 ◽  
Vol 67 (2) ◽  
pp. 89-94
Author(s):  
Elham Kazemi ◽  
Javaad Zargooshi ◽  
Mozhgan Fatahi Dehpahni ◽  
Hamid-Reza Mohammadi Motlagh ◽  
Marzieh Kaboudi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Erectile Dysfunction ◽  
Pyruvate Dehydrogenase ◽  
Computational Study ◽  
Regulatory Protein ◽  
Three Dimensional ◽  
Pyruvate Dehydrogenase Kinase ◽  
Sexual Disorders ◽  
Pcr Analysis ◽  
Pyruvate Dehydrogenase Kinase 4

Erectile dysfunction (ED) is one of the most common sexual disorders in men. During the past 30 years, there has been no new drug development for ED. Thus, exploring the genetic basis of ED deserves further study, in hope of developing new pharmacological treatments for ED. In this study, Real-Time PCR analysis was used to assess the expression of androgen regulatory protein (Andpro) and pyruvate dehydrogenase kinase 4 (Pdk4) genes in ED. For this purpose, the experiment was performed on 20 men with severe ED and 20 potent men. IIEF-15 was used to determine the ED severity. The study was conducted in the Department of Sexual Medicine of the Kermanshah University of Medical Sciences, Kermanshah, Iran. The EDTA-Na vacuum blood tube was taken from ED patients and controls. Informed consent was obtained from all participants. After blood sampling, RNA was extracted from whole blood. Then cDNA was synthesized. The gene expression was analyzed through the qPCR method. The ß-actin was used as a reference gene. To further study these two proteins, their three-dimensional structures were predicted through I-TASSER. Compared with controls, in ED patients, the expression of the Andpro gene decreased, while the expression of the Pdk4 gene increased (p<0.01). Predicting the structure of the protein showed that Pyruvate Dehydrogenase Kinase 4 had a double subunit and androgen-regulated protein had a single subunit.

Effect of high-intensity training on exercise-induced gene expression specific to ion homeostasis and metabolism

2003 ◽  
Vol 95 (3) ◽  
pp. 1201-1206 ◽  
Author(s):  
Nikolai Nordsborg ◽  
Jens Bangsbo ◽  
Henriette Pilegaard
Keyword(s):  
Gene Expression ◽  
Pyruvate Dehydrogenase ◽  
High Intensity ◽  
Pyruvate Dehydrogenase Kinase ◽  
Training Period ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Ph Homeostasis ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
Before And After

Changes in gene expression during recovery from high-intensity, intermittent, one-legged exercise were studied before and after 5.5 wk of training. Genes related to metabolism, as well as Na+, K+, and pH homeostasis, were selected for analyses. After the same work was performed before and after the training period, several muscle biopsies were obtained from vastus lateralis muscle. In the untrained state, the Na+-K+-ATPase α1-subunit mRNA level was approximately threefold higher ( P < 0.01) at 0, 1, and 3 h after exercise, relative to the preexercise resting level. After 3-5 h of recovery in the untrained state, pyruvate dehydrogenase kinase 4 and hexokinase II mRNA levels were elevated 13-fold ( P < 0.001) and 6-fold ( P < 0.01), respectively. However, after the training period, only pyruvate dehydrogenase kinase 4 mRNA levels were elevated ( P < 0.05) during the recovery period. No changes in resting mRNA levels were observed as a result of training. In conclusion, cellular adaptations to high-intensity exercise training may, in part, be induced by transcriptional regulation. After training, the transcriptional response to an exercise bout at a given workload is diminished.

scholarly journals Fasting and Glucagon Stimulate Gene Expression of Pyruvate Dehydrogenase Kinase 4 in Chickens

2017 ◽  
Vol 54 (4) ◽  
pp. 292-295 ◽  
Author(s):  
Kazuhisa Honda ◽  
Shoko Takagi ◽  
Kiyotaka Kurachi ◽  
Haruka Sugimoto ◽  
Takaoki Saneyasu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Kinase ◽  
Pyruvate Dehydrogenase Kinase 4

scholarly journals Reactive oxygen species-dependent regulation of pyruvate dehydrogenase kinase-4 in white adipose tissue

2020 ◽  
Vol 318 (1) ◽  
pp. C137-C149 ◽  
Author(s):  
Logan K. Townsend ◽  
Alyssa J. Weber ◽  
Pierre-Andre Barbeau ◽  
Graham P. Holloway ◽  
David C. Wright
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Pyruvate Dehydrogenase ◽  
Acute Exercise ◽  
Pyruvate Dehydrogenase Kinase ◽  
Oxygen Species ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
Exercise Induced

Reactive oxygen species (ROS) are important signaling molecules mediating the exercise-induced adaptations in skeletal muscle. Acute exercise also drives the expression of genes involved in reesterification and glyceroneogenesis in white adipose tissue (WAT), but whether ROS play any role in this effect has not been explored. We speculated that exercise-induced ROS would regulate acute exercise-induced responses in WAT. To address this question, we utilized various models to alter redox signaling in WAT. We examined basal and exercise-induced gene expression in a genetically modified mouse model of reduced mitochondrial ROS emission [mitochondrial catalase overexpression (MCAT)]. Additionally, H2O2, various antioxidants, and the β3-adrenergic receptor agonist CL316243 were used to assess gene expression in white adipose tissue culture. MCAT mice have reduced ROS emission from WAT, enlarged WAT depots and adipocytes, and greater pyruvate dehydrogenase kinase-4 ( Pdk4) gene expression. In WAT culture, H2O2 reduced glyceroneogenic gene expression. In wild-type mice, acute exercise induced dramatic but transient increases in Pdk4 and phosphoenolpyruvate carboxykinase ( Pck1) mRNA in both subcutaneous inguinal WAT and epididymal WAT depots, which was almost completely absent in MCAT mice. Furthermore, the induction of Pdk4 and Pck1 in WAT culture by CL316243 was markedly reduced in the presence of antioxidants N-acetyl-cysteine or vitamin E. Genetic and nutritional approaches that attenuate redox signaling prevent exercise- and β-agonist-induced gene expression within WAT. Combined, these data suggest that ROS represent important mediators of gene expression within WAT.

scholarly journals Activation of Liver X Receptor Regulates Substrate Oxidation in White Adipocytes

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4104-4113 ◽  
Author(s):  
Britta M. Stenson ◽  
Mikael Rydén ◽  
Knut R. Steffensen ◽  
Kerstin Wåhlén ◽  
Amanda T. Pettersson ◽  
...  
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Substrate Oxidation ◽  
Pyruvate Dehydrogenase Kinase ◽  
Tissue Mass ◽  
Metabolic Complications ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
White Adipocytes ◽  
X Receptors

Abstract Liver X receptors (LXRs) are nuclear receptors with established roles in cholesterol, lipid, and carbohydrate metabolism, although their function in adipocytes is not well characterized. Increased adipose tissue mass in obesity is associated with increased adipocyte lipolysis. Fatty acids (FA) generated by lipolysis can be oxidized by mitochondrial β-oxidation, reesterified, or released from the adipocyte. The latter results in higher circulating levels of free FAs, in turn causing obesity-related metabolic complications. However, mitochondrial β-oxidation can at least in part counteract an increased output of FA into circulation. In this study, we provide evidence that activation of LXRs up-regulates mitochondrial β-oxidation in both human and murine white adipocytes. We also show that the expression of a kinase regulating the cellular fuel switch, pyruvate dehydrogenase kinase 4 (PDK4), is up-regulated by the LXR agonist GW3965 in both in vitro differentiated human primary adipocytes and differentiated murine 3T3-L1 cells. Moreover, activation of LXR causes PDK4-dependent phosphorylation of the pyruvate dehydrogenase complex, thereby decreasing its activity and attenuating glucose oxidation. The specificity of the GW3965 effect on oxidation was confirmed by RNA interference targeting LXRs. We propose that LXR has an important role in the regulation of substrate oxidation and the switch between lipids and carbohydrates as cellular fuel in both human and murine white adipocytes.

scholarly journals Transforming Growth Factor β Mediates Drug Resistance by Regulating the Expression of Pyruvate Dehydrogenase Kinase 4 in Colorectal Cancer

2016 ◽  
Vol 291 (33) ◽  
pp. 17405-17416 ◽  
Author(s):  
Yang Zhang ◽  
Yi Zhang ◽  
Liying Geng ◽  
Haowei Yi ◽  
Wei Huo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Kinase ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
Mouse Xenograft Model

Drug resistance is one of the main causes of colon cancer recurrence. However, our understanding of the underlying mechanisms and availability of therapeutic options remains limited. Here we show that expression of pyruvate dehydrogenase kinase 4 (PDK4) is positively correlated with drug resistance of colon cancer cells and induced by 5-fluorouracil (5-FU) treatment in drug-resistant but not drug-sensitive cells. Knockdown of PDK4 expression sensitizes colon cancer cells to 5-FU or oxaliplatin-induced apoptosis in vitro and increases the effectiveness of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. In addition, we demonstrate for the first time that TGFβ mediates drug resistance by regulating PDK4 expression and that 5-FU induces PDK4 expression in a TGFβ signaling-dependent manner. Mechanistically, knockdown or inhibition of PDK4 significantly increases the inhibitory effect of 5-FU on expression of the anti-apoptotic factors Bcl-2 and survivin. Importantly, studies of patient samples indicate that expression of PDK4 and phosphorylation of Smad2, an indicator of TGFβ pathway activation, show a strong correlation and that both positively associate with chemoresistance in colorectal cancer. These findings indicate that the TGFβ/PDK4 signaling axis plays an important role in the response of colorectal cancer to chemotherapy. A major implication of our studies is that inhibition of PDK4 may have considerable therapeutic potential to overcome drug resistance in colorectal cancer patients, which warrants the development of PDK4-specific inhibitors.

scholarly journals Coenzyme A–mediated degradation of pyruvate dehydrogenase kinase 4 promotes cardiac metabolic flexibility after high-fat feeding in mice

2018 ◽  
Vol 293 (18) ◽  
pp. 6915-6924 ◽  
Author(s):  
Christopher Schafer ◽  
Zachary T. Young ◽  
Catherine A. Makarewich ◽  
Abdallah Elnwasany ◽  
Caroline Kinter ◽  
...  
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Coenzyme A ◽  
Pyruvate Dehydrogenase Kinase ◽  
Metabolic Flexibility ◽  
High Fat ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
Fat Feeding

scholarly journals The Role of Pyruvate Dehydrogenase Kinase-4 (PDK4) in Bladder Cancer and Chemoresistance

2018 ◽  
Vol 17 (9) ◽  
pp. 2004-2012 ◽  
Author(s):  
Benjamin L. Woolbright ◽  
Dharamainder Choudhary ◽  
Andrew Mikhalyuk ◽  
Cassandra Trammel ◽  
Sambantham Shanmugam ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Kinase ◽  
Pyruvate Dehydrogenase Kinase 4
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