The effect of SIRT1 knockdown on the gene expression of CoQ10 biosynthetic enzymes

Coenzyme Q10 (CoQ10) is an essential lipid-soluble antioxidant and a key component of the mitochondrial electron transport chain, playing critical roles in cellular redox homeostasis and energy metabolism. Although organ-specific differences in CoQ10 levels have been reported in humans, the mechanisms underlying tissue-specific regulation of CoQ10 remain poorly understood. Moreover, species differences in the predominant CoQ isoform limit the suitability of conventional rodent models for studying human CoQ10 metabolism, aging, and disease. In this study, we aimed to explore factors contributing to organ-specific CoQ10 levels and to establish fundamental reference data for medaka (Oryzias latipes), a vertebrate model that endogenously synthesizes CoQ10. CoQ10 concentrations in multiple organs were quantified by high-performance liquid chromatography. Levels of vitamin E and free cholesterol were also measured. Mitochondrial DNA (mtDNA) content was assessed as an index of mitochondrial abundance, and expression of CoQ10 biosynthetic enzymes, the CoQ-binding protein prosaposin (Psap), and 3-hydroxy-3-methylglutaryl-CoA reductase was analyzed by RT-qPCR. CoQ10 was detected in all organs examined, with the highest levels observed in the heart and liver, followed by the kidney and brain, and lower levels in skeletal muscle and the digestive tract. No significant sex-dependent differences were observed. CoQ10 levels were positively associated with PDSS2 expression and mtDNA content, while Psap expression showed strong positive correlations with multiple CoQ-related genes. These findings provide insight into factors associated with tissue-specific CoQ10 distribution and support medaka as a physiologically relevant model for investigating CoQ10 metabolism, oxidative stress, aging, and disease.

Effect of Ezetimibe and/or Simvastatin on Coenzyme Q10 Levels in Plasma

Endothelial dysfunction is common in patients undergoing hemodialysis (HD). However, little is known about the relationship between endothelial dysfunction and coenzyme Q10 (CoQ10) levels in HD patients. Eligible HD patients were enrolled in this study according to prespecified inclusion and exclusion criteria. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Plasma CoQ10, serum malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. The potential confounders identified by univariate analyses (P < 0.15) were selected in a stepwise multiple regression model. In total, 111 HD patients were enrolled in this study. The mean CoQ10 level was 633.53 ± 168.66 ng/mL, and endothelial dysfunction was prevalent (91.0%) using a cut-off value of 10% FMD. A significant correlation was observed between FMD and plasma CoQ10 level (r = 0.727, P < 0.001). After adjusting for potential parameters, a stepwise multivariate linear regression analysis revealed that CoQ10 level was an independent predictor of FMD (β = 0.018, P < 0.001). When CoQ10 was dichotomized using the median value (639.74 ng/mL), the conclusion remained unchanged (β = 0.584, P < 0.001). Pearson's correlation analyses revealed that plasma CoQ10 level was negatively correlated with MDA (r = -0.48, P < 0.001) and 8-OHdG (r = -0.43, P < 0.001) levels. Our data demonstrate that impaired brachial artery FMD was common in HD patients. CoQ10 level was independently associated with FMD, and oxidative stress may constitute a link between CoQ10 level and endothelial dysfunction in these patients.

Relationship between plasma coenzyme Q10, asymmetric dimethylarginine and arterial stiffness in patients with phenotypic or genotypic familial hypercholesterolemia on long-term statin therapy

IntroductionMitochondrial dysfunction is associated with increased mortality in septic shock. Coenzyme Q10 (CoQ10) is a key cofactor in the mitochondrial respiratory chain, but whether CoQ10 is depleted in septic shock remains unknown. Moreover, statin therapy may decrease CoQ10 levels, but whether this occurs acutely remains unknown. We measured CoQ10 levels in septic shock patients enrolled in a randomized trial of simvastatin versus placebo.MethodsWe conducted a post hoc analysis of a prospective, randomized trial of simvastatin versus placebo in patients with septic shock (ClinicalTrials.gov ID: NCT00676897). Adult patients with suspected or confirmed infection and the need for vasopressor support were included in the initial trial. For the current analysis, blood specimens were analyzed for plasma CoQ10 and low-density lipoprotein (LDL) levels. The relationship between CoQ10 levels and inflammatory and vascular endothelial biomarkers was assessed using either the Pearson or Spearman correlation coefficient.ResultsWe analyzed 28 samples from 14 patients. CoQ10 levels were low, with a median of 0.49 (interquartile range 0.26 to 0.62) compared to levels in healthy control patients (CoQ10 = 0.95 μmol/L ± 0.29; P < 0.0001). Statin therapy had no effect on plasma CoQ10 levels over time (P = 0.13). There was a statistically significant relationship between plasma CoQ10 levels and levels of vascular cell adhesion molecule (VCAM) (r2 = 0.2; P = 0.008), TNF-α (r2 = 0.28; P = 0.004), IL-8 (r2 = 0.21; P = 0.015), IL-10 (r2 = 0.18; P = 0.025), E-selectin (r2 = 0.17; P = -0.03), IL-1ra (r2 = 0.21; P = 0.014), IL-6 (r2 = 0.17; P = 0.029) and IL-2 (r2 = 0.23; P = 0.009). After adjusting for LDL levels, there was a statistically significant inverse relationship between plasma CoQ10 levels and levels of VCAM (r2 = 0.24; P = 0.01) (Figure 3) and IL-10 (r2 = 0.24; P = 0.02).ConclusionsCoQ10 levels are significantly lower in septic shock patients than in healthy controls. CoQ10 is negatively associated with vascular endothelial markers and inflammatory molecules, though this association diminishes after adjusting for LDL levels.

This study was conducted in order to know the impact of coenzyme Q10 (CoQ10) supplement on the muscle damage and total oxidant (TOS) enzyme levels of young skiing athletes during exercise. 15 male athletes were used for two weeks in the study. The athletes were divided into three groups: the control group and two subject groups taking 100 mg and 200 mg CoQ10. A maximal exercise program with 70-80% overload was applied to the groups for two hours every day for two weeks. Before (B.T.) and after (A.T.) the training, blood samples were taken from athletes in order to determine CoQ10, TOS and aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), glutamyl transpeptidase (GG), lactate dehydrogenase (LDH), Creatine kinase (CK) enzyme activities. HPLC kit was used to determine CoQ10 levels and TOS kit was used to determine TOS levels. When the pre-exercise and post-exercise CoQ10 levels were compared, it was seen that CoQ10 values of subject groups increased (p<0,05; p<0,01) while the control group did not show a significant difference. Also, a decrease was seen in TOS values of subject groups (p<0.01), whereas the control group showed an increase (p<0,01). In addition, significant increases (P<0.01) were obtained in the levels of AST, ALT, LDH and CK of the control group compared to those of the subject groups. Comparing CoQ10 and TOS levels by days during 2 weeks, it was found that TOS levels of control group increased; no change occurred at CoQ10 and; TOS levels of experimental groups decreased and significant increases were found in CoQ10 groups. In conclusion, CoQ10 usage may have impact on lower TOS values and liver, muscle enzyme activities of experimental group compared to control group. Key words: Training, muscle damage, CoQ10, total oxidant, enzyme activities.

Coenzyme Q (CoQ) is important not only as an essential lipid for the mitochondrial electron transport system, but also as an antioxidant. CoQ levels decrease during aging and in various diseases. Orally administered CoQ is not readily taken up in the brain, so it is necessary to develop a method to increase the amount of CoQ in neurons. CoQ is synthesized via mevalonate pathway, like cholesterol. Transferrin, insulin, and progesterone are factors used in the culture of neurons. In this study, we determined the effect of these reagents on cellular CoQ and cholesterol levels. The administration of transferrin, insulin, and progesterone increased cellular CoQ levels in undifferentiated PC12 cells. When serum was removed and only insulin was administered, intracellular CoQ levels increased. This increase was even more pronounced with concurrent administration of transferrin, insulin, and progesterone. Cholesterol level decreased by the administration of transferrin, insulin, and progesterone. Progesterone treatment lowered intracellular cholesterol levels in a concentration-dependent manner. Our findings suggest that transferrin, insulin, and progesterone may be useful in regulating CoQ levels and cholesterol levels, which are products of the mevalonate pathway.

Coenzyme Q10 (CoQ10) plays a crucial role in facilitating electron transport during oxidative phosphorylation, thus contributing to cellular energy production. Statin treatment causes a decrease in CoQ10 levels in muscle tissue as well as in serum, which may contribute to the musculoskeletal side effects. Therefore, we aimed to assess the effect of newly initiated statin treatment on serum CoQ10 levels after acute ST-elevation myocardial infarction (STEMI) and the correlation of CoQ10 levels with key biomarkers of subclinical or clinically overt myopathy. In this study, we enrolled 67 non-diabetic, statin-naïve early-onset STEMI patients with preserved renal function. Plasma CoQ10 level was determined by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC/MS-MS), while the myopathy marker serum fatty acid-binding protein 3 (FABP3) level was measured with enzyme-linked immunosorbent assay (ELISA) at hospital admission and after 3 months of statin treatment. The treatment significantly decreased the plasma CoQ10 (by 43%) and FABP3 levels (by 79%) as well as total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B100 (ApoB100), and oxidized LDL (oxLDL) levels. The change in CoQ10 level showed significant positive correlations with the changes in total cholesterol, LDL-C, ApoB100, and oxLDL levels, while it did not correlate with the change in FABP3 level. Our results prove the CoQ10-reducing effect of statin treatment and demonstrate its lipid-lowering efficacy but contradict the role of CoQ10 reduction in statin-induced myopathy.

Association of statin induced reduction in serum coenzyme Q10 level and conduction deficits in motor and sensory nerves: An observational cross-sectional study

This study seeks to evaluate the association between follicular fluid (FF) coenzyme Q10 (CoQ10) levels, embryo morphokinetics, and pregnancy rate. Sixty infertile patients who underwent intracytoplasmic sperm injection (ICSI) cycles were included in the study. For each patient, CoQ10 level of the follicular fluid was measured by high-performance liquid chromatography system. After the ICSI of each oocyte, the relationship between the level of CoQ10 content of each follicular fluid, the subsequent embryo quality, and embryo morphokinetics was investigated. The relationship between the level of CoQ10 content of each follicle and optimal time-lapse parameters for the embryos of these follicles including t5, s2, and cc2 was also analyzed. The embryos were further classified into four categories, namely, grades A, B, C, and D, according to morphokinetic parameters using t5-t2 and t5-t3 (cc3). Each follicular fluid analysis was performed for a single oocyte of a single embryo which was transferred to the patients. Additionally, follicular fluid CoQ10 levels and pregnancy rates were evaluated. Follicular fluid CoQ10 levels were significantly higher in grades A and B than grades C and D embryos (p < 0.05). The concentration of CoQ10 levels was significantly higher in the pregnant group (p < 0.05). There was no significant correlation between optimal t5 and s2 morphokinetic parameters and CoQ10 levels. However, CoQ10 levels were significantly higher in follicular fluid of embryos which had optimal cc2 (p < 0.05). High follicular fluid CoQ10 level is associated with optimal embryo morphokinetic parameters and higher pregnancy rates.

Clinical correlates of decreased plasma coenzyme Q10 levels in patients with multiple system atrophy

Our objectives were to assess the plasma coenzyme Q10 (CoQ10) levels in normal pregnancy, in pregnancy with a spontaneous contractile event, in spontaneous abortion and in threatened abortion. Six hundred and fifteen CoQ10 levels were analyzed in 483 pregnant women: 350 patients were employed to design a normal curve; 66 patients with spontaneous contractile activity underwent two or more CoQ10 analyses in different trimesters; 49 patients presented spontaneous abortion, and 18 patients threatened abortion. The normal curve of plasma CoQ10 levels rises during each trimester of pregnancy, while there is a correspondence between a low CoQ10 level and spontaneous abortion. Furthermore we found a statistically significant difference between the plasma CoQ10 value in spontaneous contractile activity, mainly in the third trimester. We found an increase in the plasma CoQ10 level in relation to the contractile activity of the uterine muscle. Further studies are necessary to explain the involvement of this marker on pregnancy in clinical practice.

Preeclampsia is a common disorder of pregnancy exhibiting abnormal plasma and placental coenzyme Q10 (CoQ10) levels when compared to normal pregnancies. To evaluate CoQ10 levels both in plasma and placenta among normal pregnant (n = 60) and preeclamptic (n = 63) primigravid women and determine the effect of high or low altitude residency. CoQ10 was determined using High Performance Liquid Chromatography (HPLC) technique and group comparisons were performed. Preeclamptic women living at high altitude displayed significantly lower CoQ10 plasma levels (0.64 +/- 0.23 vs. 0.82 +/- 0.46 micromol/L, p = 0.05). No differences were found in CoQ10 plasma levels among women living at sea level. Interestingly, plasma CoQ10 levels at low altitude in normal pregnancies were significantly lower than high altitude normal pregnancies. Compared to normal pregnancies, preeclamptic women displayed higher placental CoQ10 content, which was only significant among those living at sea level (0.120 +/- 0.07 vs. 0.076 +/- 0.04 ng/mg protein, p < 0.005). Normal pregnant women living at high altitude displayed higher placental CoQ10 content when compared to those residing at sea level (p < 0.0005). Women suffering from preeclampsia (high or low altitude) display high placental CoQ10 content, with significant low plasma CoQ10 levels among those residing in high altitude. More research is warranted to establish the cause-effect relationship between CoQ10 levels and preeclampsia.

Psychosocial stress-related changes in gene expression of norepinephrine biosynthetic enzymes in stellate ganglia of adult rats

Endogenous coenzyme Q10 (CoQ10) is a lipid-soluble antioxidant and essential for the electron transport chain. We previously demonstrated that hydrogen peroxide enhanced CoQ10 levels, whereas disruption of mitochondrial membrane potential by a chemical uncoupler suppressed CoQ10 levels, in human 143B cells. In this study, we investigated how CoQ10 levels and expression of two PDSS and eight COQ genes were affected by oligomycin, which inhibited ATP synthesis at Complex V without uncoupling the mitochondria. We confirmed that oligomycin increased the production of reactive oxygen species (ROS) and decreased mitochondria-dependent ATP production in 143B cells. We also demonstrated that CoQ10 levels were decreased by oligomycin after 42 or 48 h of treatment, but not at earlier time points. Expression of PDSS2 and COQ2–COQ9 were up-regulated after 18-hour oligomycin treatment, and the expression of PPARGC1A (PGC1-1α) elevated concurrently. Knockdown of PPARGC1A down-regulated the basal mRNA levels of PDSS2 and five COQ genes and suppressed the induction of COQ8 and COQ9 genes by oligomycin, but did not affect CoQ10 levels under these conditions. N-acetylcysteine suppressed the augmentation of ROS levels and the enhanced expression of COQ2, COQ4, COQ7, and COQ9 induced by oligomycin, but did not modulate the changes in CoQ10 levels. These results suggested that the condition of mitochondrial dysfunction induced by oligomycin decreased CoQ10 levels independent of oxidative stress. Up-regulation of PDSS2 and several COQ genes by oligomycin might be regulated by multiple mechanisms, including the signaling pathways mediated by PGC-1α and ROS, but it would not restore CoQ10 levels.