Abstract:
:In utero cocaine exposure can affect CNS development. Previous studies showed that cocaine inhibits neuronal differentiation in a dose-dependent fashion, in nerve growth factor (NGF)-stimulated PC12 cells, without affecting cell viability. NGF activates intracellular signaling proteins, specific immediate-early genes (IEG) including a transient peak of c-fos expression, and induction of late genes expression, leading to the neuronal phenotype. We hypothesized that cocaine interferes with NGF signaling. Therefore, we examined the pattern of c-fos expression in our cellular model. Time course of c-fos expression up to 72 h was determined in cells treated with NGF 20 ng/ml and cocaine 10 microgram/ml (a moderately toxic level) by RT-PCR analysis. Total RNA was isolated from cells, and levels of c-fos mRNA were estimated using gene-specific primers. In both control and experimental conditions, c-fos level was maximal at 0.5 h. In the control cells, c-fos expression declined rapidly to less than 5% of the 0.5h value, while in the cocaine-treated cells, c-fos level persisted through the 72-h exposure. Adding c-fos antisense to cells treated with NGF and cocaine resulted in significant improvement of neurite out-growth, from 28% (NGF + cocaine) to 89% (NGF + cocaine + c-fos antisense) of control differentiation after 72 h of exposure (Dunnet's T < 3.24). Inhibitory effects of cocaine on NGF-induced PC12 differentiation may be attributed to alteration of c-fos expression. Further studies will be required to examine the role of D1 receptor activation in mediating c-fos expression and to explore the effects of cocaine on other IEGs.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Zachor DA,Moore JF,Jin J,Theibert AB,Percy AKdoi
10.1006/mgme.1998.2699subject
Has Abstractpub_date
1998-05-01 00:00:00pages
62-9issue
1eissn
1096-7192issn
1096-7206pii
S1096-7192(98)92699-3journal_volume
64pub_type
杂志文章abstract:BACKGROUND AND OBJECTIVES:Policies for genetic testing in children (GTIC) focus on medical or psychosocial benefit to the child, discouraging or prohibiting carrier testing, and advising caution regarding pre-symptomatic diagnosis if no treatment exists. This study sought to understand parents' perspectives on these is...
journal_title:Molecular genetics and metabolism
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abstract::Glycogen storage disease type Ia (GSD-Ia) is caused by deleterious mutations in the glucose-6-phosphatase gene (G6PC). A molecular study of this gene was carried out in 11 Argentinean patients from 8 unrelated families. Four missense (p.Gln54Pro, p.Arg83Cys, p.Thr16Arg, and p.Tyr209Cys) and one deletion (c.79delC) mut...
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abstract:PURPOSE:To present clinical, biochemical and molecular information on six new clinically diagnosed Krabbe disease patients and assess the sensitivity of retrospective galactocerebrosidase measurement in their newborn screening samples. METHODS:Medical records were reviewed. Galactocerebrosidase activity was measured i...
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pub_type: 杂志文章
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更新日期:2012-01-01 00:00:00
abstract::Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-a...
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2009.09.003
更新日期:2010-01-01 00:00:00
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abstract::Pelizaeus-Merzbacher-like disease (PMLD) is a clinically and genetically heterogeneous neurological disorder of cerebral hypomyelination. It is clinically characterised by early onset (usually infantile) nystagmus, impaired motor development, ataxia, choreoathetoid movements, dysarthria and progressive limb spasticity...
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2011.08.032
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abstract::Brody disease is an inherited myopathy associated with a defective function of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 1 (SERCA1) protein. Mutations in the ATP2A1 gene have been reported only in some patients. Therefore it has been proposed to distinguish patients with ATP2A1 mutations, Brody disease (BD), fr...
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doi:10.1016/j.ymgme.2013.07.015
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abstract:OBJECTIVE:To evaluate glycerol phenylbutyrate (GPB) in the treatment of pediatric patients with urea cycle disorders (UCDs). STUDY DESIGN:UCD patients (n=26) ages 2months through 17years were treated with GPB and sodium phenylbutyrate (NaPBA) in two short-term, open-label crossover studies, which compared 24-hour ammo...
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doi:10.1016/j.ymgme.2011.04.004
更新日期:2011-08-01 00:00:00
abstract::The deficiency of a lysosomal enzyme, aspartylglucosaminidase, results in a lysosomal storage disorder, aspartylglucosaminuria, manifesting as progressive mental retardation. To understand tissue pathogenesis and disease progression we analyzed the developmental expression of the enzyme, especially in brain, which is ...
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pub_type: 杂志文章
doi:10.1006/mgme.1999.2872
更新日期:1999-08-01 00:00:00
abstract::Infantile neuronal ceroid lipofuscinosis (INCL, Infantile Batten disease) is an invariably fatal neurodegenerative pediatric disorder caused by an inherited mutation in the PPT1 gene. Patients with INCL lack the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1, EC 3.1.2.22), resulting in intracellular accumulat...
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更新日期:2016-02-01 00:00:00
abstract::Phenotypic expression of the deafness-associated mitochondrial A1555G mutation in the 12S rRNA gene is influenced by aminoglycosides and complex inheritance of nuclear-encoded modifier genes. The position of a major nuclear modifier gene has been localized to chromosome 8p23.1, but the identification of this gene has ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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doi:10.1016/j.ymgme.2007.10.131
更新日期:2008-04-01 00:00:00
abstract::Derivatives of 4-methylumbelliferone (4MU) are favorite substrates for the measurement of lysosomal enzyme activities in a wide variety of cell and tissue specimens. Hydrolysis of these artificial substrates at acidic pH leads to the formation of 4-methylumbelliferone, which is highly fluorescent at a pH above 10. Whe...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2010.09.008
更新日期:2011-01-01 00:00:00
abstract::2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency, also known as beta-ketothiolase deficiency, is an inborn error of ketone body utilization and isoleucine catabolism. It is caused by mutations in the ACAT1 gene and may present with metabolic ketoacidosis. In order to obtain a more comprehensive view on this di...
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pub_type: 杂志文章
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abstract::Carnitine palmitoyltransferase type 2 (CPT2) deficiency, a mitochondrial fatty acid oxidation disorder (MFAOD), is a cause of myopathy in its late clinical presentation. As for other MFAODs, its diagnosis may be evocated when blood acylcarnitine profile is abnormal. However, a lack of abnormalities or specificity in t...
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pub_type: 杂志文章
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更新日期:2018-04-01 00:00:00
abstract:INTRODUCTION:Telomeres may be considered markers of biological aging, shorter telomere length is associated with some age-related diseases; in several studies short telomere length has also been associated to obesity in adults and adolescents. However the relationship between telomere complex functions and obesity is s...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2016.04.003
更新日期:2016-06-01 00:00:00
abstract::Phytanic acid is a 3-methyl branched-chain fatty acid which originates from dietary sources. Since the 3-methyl group blocks regular beta-oxidation, it is broken down by peroxisomal alpha-oxidation. Adult Refsum disease patients accumulate phytanic acid as a result of an impairment in peroxisomal alpha-oxidation, caus...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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更新日期:2005-07-01 00:00:00