Disease relevance of ATP5J

• In a multiple regression model, plasma CF6 level (r=0.24, P=0.023) and ADMA level (r=0.26, P=0.023) were independently related to the occurrence of ischemic heart disease in hemodialysis patients [1].
• CONCLUSION: CF6 is a novel risk factor for ischemic heart disease in end-stage renal disease (ESRD) [1].
• In this study, we measured the plasma CF6 level of patients with acute myocardial infarction (AMI) to observe dynamic changes of CF6 [2].
• We showed a high plasma level of CF6 in human hypertension [3].

High impact information on ATP5J

• CONCLUSIONS: CF6 changes the gene expression profile to be proatherogenic and functions as a novel stimulator for ADMA release by enhancing its synthesis and suppressing its degradation [4].
• However, because arachidonic acid acts in the widespread fields of vascular biology, CF6 might exert profound effects in addition to vasoconstriction [4].
• Experiments with permeabilized myocytes revealed that with normal cytosolic energy reserves (mm: ATP 5, ADP 0.01, phosphocreatine (CrP) 10) fructose-1,6-bisphosphate (FBP; 1 mm) and fructose-6-phosphate (F6P; 1 mm) caused a transient increase of Ca(2+) spark frequency by 62 and 42%, respectively [5].
• OBJECTIVE: We previously showed that mitochondrial coupling factor 6 (CF6), an endogenous inhibitor of prostacyclin synthesis and a vasoconstrictor, is present on the surface of human umbilical vein endothelial cells (HUVEC) and is released outside of the cells by shear stress [6].
• Pretreatment with troglitazone or 15d-PGJ2 inhibited the shear-induced release and gene expression of CF6, whereas fenofibric acid, a PPAR-alpha ligand, had no influence on them [6].

Biological context of ATP5J

• At 3 days, the plasma level of CF6 correlated positively with the plasma CK peak value and correlated negatively with left ventricular ejection fraction [2].
• The hydrolysis activity of ATP to ADP was increased by 1.6-fold by CF6 at 10(-7) M, and efrapeptin at 10(-5) M, an inhibitor of ATP synthase, blocked it [3].
• Transfection experiments with deletional and mutational CF6 promoter constructs, and with dominant negative mutant IkappaB kinase alpha (K44M) demonstrated that shear-induced CF6 transcription was dependent on nuclear factor-kappa B (NF-kappaB) activation [6].
• Thus, the biologically active site probably resides at the C-terminal portion of CF-6 peptides [7].
• Accordingly, intravenous administration of CF-6, pCF-6, rat CF-6, and rat pCF-6 produced a modest but statistically significant increase in blood pressure and heart rate in urethane anesthetized rats, whereas the N-terminal rat pro-coupling factor-6, (24-52)-NH(2) and (33-52)-NH(2) caused no significant pressor response [7].

Anatomical context of ATP5J

• Previous studies have shown that mitochondrial coupling factor 6 (CF6) is an endogenous peptide that inhibits prostacyclin (PGI2) synthesis in vascular endothelial cells [2].
• Incubation of human umbilical vein endothelial cells (HUVECs) with an excess of free CF6 reduced by 50% the immunoreactivity for the antibody to beta-subunit of ATP synthase at the cell surface, but unaffected that for the alpha-subunit antibody [3].
• Treatment of ECV-304 and HUVEC with TNF-alpha enhanced the release of CF6 in a dose-dependent manner concomitantly with the decrease in CF6 content in the mitochondria at 24 h [8].
• We investigated the intracellular signaling mechanism for shear-induced release of CF6 in HUVEC and the effects of troglitazone and 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2), both peroxisome proliferator-activated receptor (PPAR)-gamma ligands, on it [6].
• Immunofluorescence microscopy of both ECV 304 and HUVECs confirmed the surface-associated immunoreactivity of anti-CF6 antibody on the plasma membrane [9].

Associations of ATP5J with chemical compounds

• We investigated cross-sectionally the association between coupling factor 6 (CF6), an endogenous inhibitor of prostacyclin synthesis, and cardiovascular events in 95 hemodialysis patients [1].
• Plasma CF6 level was positively correlated with serum creatinine level (r=0.36, P < 0.01) and was reduced after dialysis (P < 0.05) [1].
• At 24 h after onset of AMI, the plasma CF6 levels correlated positively with plasma total cholesterol levels and low-density lipoprotein levels [2].
• Coupling factor 6 (CF6), a component of adenosine triphosphate (ATP) synthase, is circulating and functions as an endogenous vasoconstrictor by inhibiting cytosolic phospholipase A2 [3].
• Arachidonic acid release was suppressed by CF6, and it was reversed by efrapeptin at 10(-5) M or beta-subunit antibody or ADP at 10(-7) M [3].

Other interactions of ATP5J

• Coupling factor 6 (F6) is a component of mitochondrial ATP synthase which is required for the interactions of the catalytic and proton-translocating segments [10].

Analytical, diagnostic and therapeutic context of ATP5J

• RESULTS: Plasma levels of CF6 and ADMA were threefold higher in hemodialysis patients than in control individuals, and there was a positive correlation between these two compounds (r=0.25, P < 0.05) [1].
• METHODS: Plasma CF6 level was measured by radioimmunoassay, whereas plasma ADMA level by high-performance liquid chromatography (HPLC) [1].
• At 7 days after the onset of AMI, the plasma CF6 levels of patients who received no reperfusion were significantly higher than those of patients who received a successful reperfusion [2].
• METHODS AND RESULTS: The release and gene expression of CF6 in HUVEC were enhanced by shear stress at 25 dyn/cm2, measured by radioimmunoassay and real-time RT-PCR, respectively [6].
• Flow cytometry analysis revealed that the cell surface-associated CF6 was significantly increased at 24 h after TNF-alpha in a dose-dependent manner [8].

References