Eicosapentaenoic acid increases cytochrome P-450 2J2 gene expression and epoxyeicosatrienoic acid production via peroxisome proliferator-activated receptor γ in endothelial cells

Summaryω-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have beneficial effects on cardiovascular diseases. Cytochrome P-450 (CYP) 2J2 that is expressed in endothelial cells metabolizes arachidonic acids to biologically active epoxyeicosatrienoic acids (EETs) that possess anti-inflammatory and anti-thrombotic effects.We studied the effects of EPA and DHA on the expression of CYP 2J2 mRNA by reverse transcription-polymerase chain reaction in cultured human umbilical vein endothelial cells and found that EPA, but not DHA, increased the expression of CYP 2J2 mRNA in a dose-dependent and a time-dependent manner. EPA-induced CYP 2J2 expression was significantly inhibited by pretreatment with a peroxisome proliferator-activated receptor (PPAR) γ antagonist, GW9662. EPA, but not DHA, caused a significant increase in cellular levels of 11,12-dihydroxyeicosatrienoic acid that is a stable metabolite of 11,12-EET, which was blocked by pretreatment with GW9662.These data demonstrate that EPA increases CYP 2J2 mRNA expression and 11,12-EET production via PPARγ in endothelial cells and indicate a novel protective role of EPA and PPARγ against vascular inflammation

X-linked Charcot-Marie-Tooth disease (CMTX) in a severely affected female patient with scattered lesions in cerebral white matter

Charcot-Marie-Tooth neuropathy (CMT) is an inherited degenerative disorder of the peripheral nervous system that results in slowly progressive distal muscle weakness, atrophy and loss of proprioception in the affected areas. X-linked CMT (CMTX) has been localized to the pericentric region of the X chromosome. CMTX neuropathy is usually associated with mutations in exon 2 of the gap junction protein β1 (GJB1) gene. GJB1 is a gap junction protein expressed in various cells including oligodendrocytes, astrocytes and myelinating schwann cells. Here, we report a female case of CMTX with a GJB1 mutation. The patient was severely clinically affected and exhibited both the features of demyelination and axonopathy. This is the first female patient with CMTX who showed permanent atypical scattered lesions in cerebral white matter of the brain on T2-weighted magnetic resonance images (MRI), which is very rare. The existence of a female patient with severe clinical symptoms may show that gain of function mechanism also leads to the disorders seen in these patients

Downbeat positioning nystagmus is a common clinical feature despite variable phenotypes in an FHM1 family

Clinical examination and mutational analysis were carried out in three patients of a Japanese familial hemiplegic migraine (FHM) pedigree. Each affected member demonstrated a broad clinical spectrum that included hemiplegic migraine with progressive cerebellar ataxia, migraine without aura, and episodic ataxia. Despite this variability, all members exhibited marked downbeat positioning nystagmus, and magnetic resonance images (MRI) all showed cerebellar atrophy predominantly of the cerebellar vermis. All affected members had a T666M missense mutation in the protein encoded by the CACNA1A gene (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit). Although clinical features associated with the T666M CACNA1A mutation are highly variable, downbeat positioning nystagmus may be an important clinical feature of this disease