Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.99.3 (acyl-CoA dehydrogenase)
 1,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The retinal pigment epithelium (RPE) and the choriocapillaris are affected early in the retinopathy associated with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. RPE in culture possesses the machinery needed for mitochondrial fatty acid beta-oxidation in vitro. To further elucidate pathogenesis of LCHAD retinopathy, we performed immunohistochemistry of the human eye and brain with antibodies to beta-oxidation enzymes. Human eye and brain sections were stained with antibodies to medium-chain (MCAD) and very long-chain acyl-CoA dehydrogenase (VLCAD), short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), and mitochondrial trifunctional protein (MTP) harboring LCHAD. Antibodies to 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) and cytochrome c oxidase subunit I (COX I) were used as a reference. VLCAD, MTP, MCAD, SCHAD, MHBD, and COX I antibodies labeled most retinal layers and tissues of the human eye actively involved in oxidative metabolism (extraocular and intraocular muscle, the RPE, the corneal endothelium, and the ciliary epithelium). MTP and COX I antibodies labeled the inner segments of photoreceptors. The choriocapillaris was labeled only with SCHAD and MCAD antibodies. In the brain, the choroid plexus and nuclei of the brain stem were most intensely labeled with beta-oxidation antibodies, whereas COX I antibodies strongly labeled neurons in several regions of the brain. Mitochondrial fatty acid beta-oxidation likely plays a role in ocular energy production in vivo. The RPE rather than the choriocapillaris could be the critical affected cell layer in LCHAD retinopathy. Reduced energy generation in the choroid plexus may contribute to the cerebral edema observed in patients with beta-oxidation defects.
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PMID:Mitochondrial fatty acid beta-oxidation in the human eye and brain: implications for the retinopathy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. 1534 68

The effects of acute perfluorododecanoic acid (PFDoA) exposure on the induction of oxidative stress and alteration of mitochondrial gene expression were studied in the livers of female zebrafish (Danio rerio). Female zebrafish were exposed to PFDoA via a single intraperitoneal injection (0, 20, 40, or 80 microg PFDoA/g body weight) and were then sacrificed 48 h, 96 h, or seven days post-PFDoA administration. PFDoA-treated fish exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. Glutathione (GSH) content and catalase (CAT) activity decreased significantly at 48 h post-injection while superoxide dismutase (SOD) activity was initially decreased at 48 h post-injection but was then elevated by seven days post-injection. The activity of glutathione peroxidase (GPx) increased at 48 h and seven days compared to control fish, although the increased level at seven days post-injection was decreased compared to the level at 48 h post-injection. Lipid peroxidation levels were increased at seven days post-injection, while no apparent induction was observed at 48 h or 96 h post-injection. The mRNA expression of medium-chain fatty acid dehydrogenase (MCAD) was induced, while the transcriptional expression of liver fatty acid binding protein (L-FABP), peroxisome proliferating activating receptor alpha (PPARalpha), carnitine palmitoyl-transferase I (CPT-I), uncoupling protein 2 (UCP-2), and Bcl-2 were significantly inhibited. Furthermore, the transcriptional expression of peroxisomal fatty acyl-CoA oxidase (ACOX), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain acyl-CoA dehydrogenase (LCAD) did not exhibit significant changes following PFDoA treatment. No significant changes were noted in the transcriptional expression of genes involved in mitochondrial respiratory chain and ATP synthesis, including cytochrome c oxidase subunit I (COXI), NADH dehydrogenase subunit I (NDI), and ATP synthase F0 subunit 6 (ATPo6). These results demonstrate that turbulence of fatty acid beta-oxidation and oxidative stress responses were involved in the PFDoA-induced hepatotoxicity.
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PMID:Induction of time-dependent oxidative stress and related transcriptional effects of perfluorododecanoic acid in zebrafish liver. 1876 Aug 46