PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-6 (6)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
Document Types
1.  Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on a high-fat, high-sugar diet 
Cell metabolism  2013;18(4):10.1016/j.cmet.2013.09.004.
SUMMARY
Obesity is associated with a chronic, low-grade, systemic inflammation that may contribute to the development of insulin resistance and type 2 diabetes. Resveratrol, a natural compound with anti-inflammatory properties, is shown to improve glucose tolerance and insulin sensitivity in obese mice and humans. Here we tested the effect of a 2-year resveratrol administration on pro-inflammatory profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in white adipose tissue (WAT) from rhesus monkeys. Eighty mg/day of resveratrol for 12-month followed by 480 mg/day for the second year decreased adipocyte size, increased sirtuin 1 expression, decreased NF-κB activation and improved insulin sensitivity in visceral but not subcutaneous WAT from HFS-fed animals. These effects were reproduced in 3T3-L1 adipocytes cultured in media supplemented with serum from monkeys fed HFS +/− resveratrol diets. In conclusion, chronic administration of resveratrol exerts beneficial metabolic and inflammatory adaptations in visceral WAT from diet-induced obese monkeys.
doi:10.1016/j.cmet.2013.09.004
PMCID: PMC3832130  PMID: 24093677
2.  Plasma membrane coenzyme Q: evidence for a role in autism 
Background
The Voltage Dependent Anion Channel (VDAC) is involved in control of autism. Treatments, including coenzyme Q, have had some success on autism control.
Data sources
Correlation of porin redox activity and expression of autism is based on extensive literature, especially studies of antibodies, identification of cytosolic nicotinamide adenine dinucleotide reduced (NADH) dehydrogenase activity in the VDAC, and evidence for extreme sensitivity of the dehydrogenase to a mercurial. Evidence for a coenzyme Q requirement came from extraction and analog inhibition of NADH ferricyanide reductase in the erythrocyte plasma membrane, done in 1994, and reinterpreted when it was identified in VDAC in 2004. The effects of ubiquinol (the QH2 – reduced form of coenzyme Q) in children with autism were studied.
Results
A new role for coenzyme Q in the porin channels has implications on autism. Ubiquinol, the more active form of coenzyme Q, produces favorable response in children with autism. Agents which affected electron transport in porin show parallel effects in autism.
Conclusion
We propose a hypothesis that autism is controlled by a coenzyme Q-dependent redox system in the porin channels; this conclusion is based on the effects of agents that positively or negatively affect electron transport and the symptoms of autism. The full understanding of the mechanism of their control needs to be established.
doi:10.2147/BTT.S53375
PMCID: PMC4043426
porin; channel; oxidation; reduction; autism
3.  Effect of vanillic acid on COQ6 mutants identified in patients with coenzyme Q10 deficiency☆ 
Biochimica et Biophysica Acta  2014;1842(1):1-6.
Human COQ6 encodes a monooxygenase which is responsible for the C5-hydroxylation of the quinone ring of coenzyme Q (CoQ). Mutations in COQ6 cause primary CoQ deficiency, a condition responsive to oral CoQ10 supplementation. Treatment is however still problematic given the poor bioavailability of CoQ10. We employed S. cerevisiae lacking the orthologous gene to characterize the two different human COQ6 isoforms and the mutations found in patients. COQ6 isoform a can partially complement the defective yeast, while isoform b, which lacks part of the FAD-binding domain, is inactive but partially stable, and could have a regulatory/inhibitory function in CoQ10 biosynthesis. Most mutations identified in patients, including the frameshift Q461fs478X mutation, retain residual enzymatic activity, and all patients carry at least one hypomorphic allele, confirming that the complete block of CoQ biosynthesis is lethal. These mutants are also partially stable and allow the assembly of the CoQ biosynthetic complex. In fact treatment with two hydroxylated analogues of 4-hydroxybenzoic acid, namely, vanillic acid or 3-4-hydroxybenzoic acid, restored the respiratory growth of yeast Δcoq6 cells expressing the mutant huCOQ6-isoa proteins. These compounds, and particularly vanillic acid, could therefore represent an interesting therapeutic option for COQ6 patients.
Highlights
•Human COQ6 alleles are hypomorphic•Human COQ6 mutations are catalytically inactive but stable•4-Hydroxybenzoate analogues can bypass the CoQ deficiency due to COQ6 mutations•Vanillic acid could represent a potential therapeutic agent for this condition
doi:10.1016/j.bbadis.2013.10.007
PMCID: PMC3898990  PMID: 24140869
COQ6, flavin-dependent monooxygenase; CoQ, coenzyme Q; CoQ10, coenzyme Q10; 4HB, 4-hydroxybenzoate; VA, vanillic acid; 3,4 diHB, 3,4 dihydroxybenzoic acid; SRNS, steroid resistant nephrotic syndrome; CYC1, cytochrome c1; pHBH, para-hydroxybenzoate hydroxylase; FAD, flavin adenine dinucleotide; COQ8-ADCK3, aarF domain containing kinase 3; Coenzyme Q; Vanillic acid; COQ6; Steroid-resistant nephrotic syndrome
4.  COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness  
The Journal of Clinical Investigation  2011;121(5):2013-2024.
Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of end-stage renal failure. Identification of single-gene causes of SRNS has generated some insights into its pathogenesis; however, additional genes and disease mechanisms remain obscure, and SRNS continues to be treatment refractory. Here we have identified 6 different mutations in coenzyme Q10 biosynthesis monooxygenase 6 (COQ6) in 13 individuals from 7 families by homozygosity mapping. Each mutation was linked to early-onset SRNS with sensorineural deafness. The deleterious effects of these human COQ6 mutations were validated by their lack of complementation in coq6-deficient yeast. Furthermore, knockdown of Coq6 in podocyte cell lines and coq6 in zebrafish embryos caused apoptosis that was partially reversed by coenzyme Q10 treatment. In rats, COQ6 was located within cell processes and the Golgi apparatus of renal glomerular podocytes and in stria vascularis cells of the inner ear, consistent with an oto-renal disease phenotype. These data suggest that coenzyme Q10–related forms of SRNS and hearing loss can be molecularly identified and potentially treated.
doi:10.1172/JCI45693
PMCID: PMC3083770  PMID: 21540551
5.  MITOCHONDRIAL BIOGENESIS AND HEALTHY AGING 
Experimental gerontology  2008;43(9):813-819.
Aging is associated with an overall loss of function at the level of the whole organism that has origins in cellular deterioration. Most cellular components, including mitochondria, require continuous recycling and regeneration throughout the lifespan. Mitochondria are particularly susceptive to damage over time as they are the major bioenergetic machinery and source of oxidative stress in cells. Effective control of mitochondrial biogenesis and turnover, therefore, becomes critical for the maintenance of energy production, the prevention of endogenous oxidative stress and the promotion of healthy aging. Multiple endogenous and exogenous factors regulate mitochondrial biogenesis through the peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). Activators of PGC-1α include nitric oxide, CREB and AMPK. Calorie restriction (CR) and resveratrol, a proposed CR mimetic, also increase mitochondrial biogenesis through activation of PGC-1α. Moderate exercise also mimics CR by inducing mitochondrial biogenesis. Negative regulators of PGC-1α such as RIP140 and 160MBP suppress mitochondrial biogenesis. Another mechanism involved in mitochondrial maintenance is mitochondrial fission/fusion and this process also involves an increasing number of regulatory proteins. Dysfunction of either biogenesis or fission/fusion of mitochondria is associated with diseases of the neuromuscular system and aging, and a greater understanding of the regulation of these processes should help us to ultimately control the aging process.
doi:10.1016/j.exger.2008.06.014
PMCID: PMC2562606  PMID: 18662766
6.  Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending lifespan 
Cell metabolism  2008;8(2):157-168.
SUMMARY
A small molecule that safely mimics the ability of dietary restriction (DR) to delay age-related diseases in laboratory animals is greatly sought after. We and others have shown that resveratrol mimics effects of DR in lower organisms. In mice, we find that resveratrol induces gene expression patterns in multiple tissues that parallel those induced by DR and every-other-day feeding. Moreover, resveratrol-fed elderly mice show a marked reduction in signs of aging including reduced albuminuria, decreased inflammation and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at 12 months of age. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started mid-life.
doi:10.1016/j.cmet.2008.06.011
PMCID: PMC2538685  PMID: 18599363

Results 1-6 (6)