ABSTRACT
Objective: To explore the changes of pyruvate dehydrogenase (PDH) activity and pyruvate dehydrogenase kinase 4 (PDK4) expression in the end-stage renal disease (ESRD) patients' skeletal muscles. Methods: Skeletal muscle samples were collected from non-chronic kidney disease (non-CKD) patients and ESRD patients. PDH activity was detected by ELISA assay. Real-time qPCR was performed to examine gene transcription levels of PDK1-PDK4 and PDH subunits. Western blotting analysis was used to detect protein expression levels of PDK1 and PDK4. Results: There were no demographic differences between two groups of patients. Plasma creatinine and urea nitrogen were significantly elevated in ESRD group (both P<0.05), while estimated glomerular filtration rate, hemoglobin and plasma albumin in ESRD group were significantly lower than those in non-CKD group (all P<0.05). Skeletal muscle PDH activity in ESRD group was markedly lower than that in non-CKD group (P=0.014). There were no differences in PDK1-PDK4 and PDH subunits mRNA transcription levels between ESRD and non-CKD group. PDK4 protein expression was significantly higher than that in non-CKD group (P=0.000). Conclusion: The decreased PDH activity in ESRD patients' skeletal muscle may be related to up-regulation of PDK4.
ABSTRACT
Objective·To explore the changes of pyruvate dehydrogenase (PDH) activity and pyruvate dehydrogenase kinase 4 (PDK4) expression in the end-stage renal disease (ESRD) patients' skeletal muscles. Methods·Skeletal muscle samples were collected from non-chronic kidney disease (non-CKD) patients and ESRD patients. PDH activity was detected by ELISA assay. Real-time qPCR was performed to examine gene transcription levels of PDK1-PDK4 and PDH subunits.Western blotting analysis was used to detect protein expression levels of PDK1 and PDK4. Results·There were no demographic differences between two groups of patients. Plasma creatinine and urea nitrogen were significantly elevated in ESRD group (both P<0.05), while estimated glomerular filtration rate, hemoglobin and plasma albumin in ESRD group were significantly lower than those in non-CKD group (all P<0.05).Skeletal muscle PDH activity in ESRD group was markedly lower than that in non-CKD group(P=0.014).There were no differences in PDK1-PDK4 and PDH subunits mRNA transcription levels between ESRD and non-CKD group.PDK4 protein expression was significantly higher than that in non-CKD group (P=0.000). Conclusion·The decreased PDH activity in ESRD patients' skeletal muscle may be related to up-regulation of PDK4.
ABSTRACT
Vascular calcification, abnormal mineralization of the vessel wall, is frequently associated with aging, atherosclerosis, diabetes mellitus, and chronic kidney disease. Vascular calcification is a key risk factor for many adverse clinical outcomes, including ischemic cardiac events and subsequent cardiovascular mortality. Vascular calcification was long considered to be a passive degenerative process, but it is now recognized as an active and highly regulated process similar to bone formation. However, despite numerous studies on the pathogenesis of vascular calcification, the mechanisms driving this process remain poorly understood. Pyruvate dehydrogenase kinases (PDKs) play an important role in the regulation of cellular metabolism and mitochondrial function. Recent studies show that PDK4 is an attractive therapeutic target for the treatment of various metabolic diseases. In this review, we summarize our current knowledge regarding the mechanisms of vascular calcification and describe the role of PDK4 in the osteogenic differentiation of vascular smooth muscle cells and development of vascular calcification. Further studies aimed at understanding the molecular mechanisms of vascular calcification will be critical for the development of novel therapeutic strategies.
Subject(s)
Aging , Atherosclerosis , Bone Morphogenetic Proteins , Diabetes Mellitus , Metabolic Diseases , Metabolism , Mitochondria , Mortality , Muscle, Smooth, Vascular , Osteogenesis , Oxidoreductases , Phosphotransferases , Pyruvic Acid , Renal Insufficiency, Chronic , Risk Factors , Vascular CalcificationABSTRACT
Recent studies indicate that exercise with a low muscle glycogen state enhances exercise-induced metabolic adaptation. However, it is unclear whether metabolic adaptation is involved with muscle glycogen depletion level. In this study, we investigated the effects of prior muscle glycogen depletion level on metabolic response during acute continuous exercise. Seven men completed two experimental trials consisting of two exercise sessions per day. During the first session, participants performed either intermittent exercise (IE) at VO<sub>2</sub>max (the IE-CE trial) or continuous exercise (CE) at lactate threshold (the CE-CE trial). During the second session, participants performed 60 minutes of CE at lactate threshold. During this second session, fatty acid oxidation (FAO) was calculated. To determine muscle glycogen content and PGC-1α and PDK-4 mRNA abundance, muscle biopsies were taken at rest after the first session and 2 hours after the second session. After the first session, muscle glycogen content was significantly lower in the IE-CE trial (38.1±5.0 mmol/kg w.w.) than in the CE-CE trial (56.7±10.2 mmol/kg w.w.), <i>P</i><0.05. FAO was higher in the IE-CE trial than the CE-CE trial at baseline and 15 minutes after the second session (both <i>P</i><0.05). PGC-1α mRNA abundance increased after exercise (IE-CE, 5.9±2.5; CE-CE, 2.6±1.3-fold; <i>P</i><0.1). PDK-4 mRNA abundance increased significantly after exercise (IE-CE, 22.2±8.8; CE-CE, 31.5±10.6-fold; <i>P</i><0.05). PGC-1α and PDK-4 mRNA were not significantly different between the trials. In conclusion, continuous exercise with a slightly muscle glycogen-depleted state induced similar level of PGC-1α and PDK-4 mRNA expression, but attenuated FAO, compared to exercise with a moderate muscle glycogen-depleted state.