Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.12.2 (
MEK
)
18,161
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The cardiofaciocutaneous (CFC) syndrome is characterized by congenital heart defect, developmental delay, peculiar facial appearance with bitemporal constriction, prominent forehead, downslanting palpebral fissures, curly sparse hair and abnormalities of the skin. CFC syndrome phenotypically overlaps with Noonan and Costello syndromes. Mutations of several genes (PTPN11, HRAS, KRAS, BRAF,
MEK1
and
MEK2
), involved in the mitogen-activated protein kinase (MAPK) pathway, have been identified in CFC-Costello-Noonan patients.
Coenzyme Q10
(
CoQ10
), a lipophilic molecule present in all cell membranes, functions as an electron carrier in the mitochondrial respiratory chain, where it transports electrons from complexes I and II to complex III.
CoQ10
deficiency is a rare treatable mitochondrial disorder with various neurological (cerebellar ataxia, myopathy, epilepsy, mental retardation) and extraneurological (cardiomyopathy, nephropathy) signs that are responsive to
CoQ10
supplementation. We report the case of a 4-year-old girl who presented a CFC syndrome, confirmed by the presence of a pathogenic R257Q BRAF gene mutation, together with a muscular
CoQ10
deficiency. Her psychomotor development was severely impaired, hindered by muscular hypotonia and ataxia, both improving remarkably after
CoQ10
treatment. This case suggests that there is a functional connection between the MAPK pathway and the mitochondria. This could be through the phosphorylation of a nuclear receptor essential for
CoQ10
biosynthesis. Another hypothesis is that K-Ras, one of the proteins composing the MAPK pathway, might be recruited into the mitochondria to promote apoptosis. This case highlights that
CoQ10
might contribute to the pathogenesis of CFC syndrome.
...
PMID:Cardiofaciocutaneous (CFC) syndrome associated with muscular coenzyme Q10 deficiency. 1770 71
This study investigates the effects and possible mechanism of
coenzyme Q10
(
CoQ10
) on endogenous glutamate release in the cerebral cortex nerve terminals of rats.
CoQ10
inhibited the release of glutamate evoked by the K+ channel blocker 4-aminopyridine (4-AP).
CoQ10
reduced the depolarization-induced increase in cytosolic [Ca2+]c but did not alter the 4-AP-mediated depolarization. The effect of
CoQ10
on evoked glutamate release was abolished by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) Ca2+ channels and
mitogen-activated protein kinase kinase
(
MEK
). In addition,
CoQ10
decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, a major presynaptic substrate for ERK. Moreover, the inhibition of glutamate release by
CoQ10
was strongly attenuated in mice without synapsin I. These results suggest that
CoQ10
inhibits glutamate release from cortical synaptosomes in rats through the suppression of the presynaptic voltage-dependent Ca2+ entry and ERK/synapsin I signaling pathway.
...
PMID:Coenzyme Q10 inhibits the release of glutamate in rat cerebrocortical nerve terminals by suppression of voltage-dependent calcium influx and mitogen-activated protein kinase signaling pathway. 2316 55
Our recent studies revealed that supplementation with the reduced form of
coenzyme Q10
(CoQ
10
H
2
) inhibits oxidative stress and slows the process of aging in senescence-accelerated mice. CoQ
10
H
2
inhibits adipocyte differentiation and regulates lipid metabolism. In the present study, we show that dietary supplementation with CoQ
10
H
2
significantly reduced white adipose tissue content and improved the function of brown adipose tissue by regulating expression of lipid metabolism-related factors in KKAy mice, a model of obesity and type 2 diabetes. In the liver, CoQ
10
H
2
reduced cytoplasmic Ca
2+
levels and consequently inhibited the phosphorylation of CaMKII. CoQ
10
H
2
also regulated the activity of the transcription factor C-FOS and inhibited gene expression of PDE4, a cAMP-degrading enzyme, via the CaMKII-
MEK1
/2-ERK1/2 signaling pathway, thereby increasing intracellular cAMP. This increased cAMP activated AMPK, enhanced oxidative decomposition of lipids, and inhibited de novo synthesis of fatty acids, inhibiting the development and progression of obesity and type 2 diabetes. These results suggest that CoQ
10
H
2
supplementation may be useful as a treatment for metabolic disorders associated with obesity.
...
PMID:Coenzyme Q10 Improves Lipid Metabolism and Ameliorates Obesity by Regulating CaMKII-Mediated PDE4 Inhibition. 2881 12
