Individuals who carry the most active alcohol dehydrogenase (ADH) isoforms are protected against alcoholism. This work addresses mechanism by which a high ADH activity leads to low ethanol intake in animals. Male and female drinker rats (UChB) were allowed access 10% for 1 h. Females showed 70% higher hepatic displayed 60% lower voluntary than males. Following administration (1 g/kg ip), females generated transient blood acetaldehyde increase ("burst") with levels that 2.5-fold greater males...

The adrenoleukodystrophy protein (ALDP) and the 70-kDa peroxisomal membrane are half ATP-binding cassette (ABC) transporters in human peroxisome membrane. Both implicated genetic disorders of biogenesis function. Proteins homologous to ALDP have been discovered other eukaryotic organisms form a growing group ABC transporters. Amino acid sequence alignment these reveals several motifs that highly conserved both location. Here we characterize two these, designated EAA-like loop1 motifs. We...

Humans who carry a point mutation in the gene coding for alcohol dehydrogenase-lB (ADH1B*2; Arg47His) are markedly protected against alcoholism. Although this results 100-fold increase enzyme activity, it has not been reported to cause higher levels of acetaldehyde, metabolite ethanol known deter intake. Hence, mechanism by which confers protection alcoholism is unknown. To study protective effect, wild-type rat cDNA encoding rADH-47Arg was mutated encode rADH-47His, mimicking human...

Background: Some gene polymorphisms strongly protect against the development of alcoholism. A large proportion East Asians carry a protective inactivating mutation in aldehyde dehydrogenase (ALDH2*2). These subjects display high levels blood acetaldehyde when consuming alcohol, condition that exerts 66 to 99% protection alcohol abuse and Present knowledge allows incorporation therapeutic genes can modify expression disease predisposing genes, an effect last from months years. In line with...

Dependence on alcohol, a most widely used drug, has heritability of 50–60%. Wistar-derived rats selectively bred as low-alcohol consumers for many generations present an allele (Aldh22) mitochondrial aldehyde dehydrogenase that does not exist in high-alcohol consumers, which mostly carry the Aldh21 allele. The enzyme coded by Aldh22 four- to five-fold lower affinity NAD+ than Aldh21. study was designed determine whether these polymorphisms account differences voluntary ethanol intake and...

Loxoscelism is the envenomation caused by bite of Loxosceles spp. spiders. It entails severe necrotizing skin lesions, sometimes accompanied systemic reactions and even death. There are no diagnostic means treatment mostly palliative. The main toxin, found in several isoforms venom, sphingomyelinase D (SMD), a phospholipase that has been used to generate antibodies intended for medical applications. Nucleic acid aptamers promising alternative antibodies. Aptamers may be isolated from...

Genetic factors influence alcohol consumption and alcoholism. A number of groups have bred drinker non rat strains, but genetic determinants remain unknown. The University Chile lines UChA (low drinkers) UChB (high display differences in the relative K(m) for NAD+ mitochondrial aldehyde dehydrogenase (ALDH2) no V(max) differences. may be due to changes or coding ALDH2. We investigated whether there are regions ALDH2 cDNA these Aldh2 genotype predicts phenotype NAD+. Liver was prepared,...

Animals selectively bred for a desirable trait retain wanted genes but exclude that may counteract the expression of former. The possible interactions between selected and excluded cannot be readily studied in transgenic or knockout animals addressed by crossing opposite traits studying F2 offspring. Ninety-seven percent Wistar-derived rats their voluntary low-alcohol consumption display mutated nuclear allele aldehyde dehydrogenase Aldh22 encodes an enzyme with low affinity NAD+, whereas...

Ribozyme genes were designed to reduce voluntary alcohol drinking in a rat model of dependence. Acetaldehyde generated from the liver is metabolized by mitochondrial aldehyde dehydrogenase (ALDH2) such that diminishing ALDH2 activity leads aversive effects blood acetaldehyde upon intake. A stepwise approach was followed design encoding ribozymes targeted mRNA. In vitro studies accessibility oligonucleotides identified suitable target sites mRNA, one which fulfilled hammerhead and hairpin...

Alcohol is detoxified in the liver by oxidizing enzymes that require nicotinamide adenine dinucleotide (NAD+) such that, rat, availability of NAD+ contributes to control voluntary ethanol intake. The UChA and UChB lines Wistar rats drink low high amounts respectively differ capacity their mitochondria oxidize NADH into NAD+. This function resides complex I respiratory chain its variation linked genes transmitted through maternal line. aim this study was identify genetic basis for difference...

A minimum of 460 nucleotides 16S ribosomal RNA are needed to fold the target site for E. coli protein S4, although a much smaller region within this large domain is protected from chemical reagents by protein. Starting with 531-nucleotide tRNA fragment, cycles mutagenesis, selection and amplification ('in vitro evolution') were used obtain pool 30 sequences selected S4 recognition but approximately 30% different wild type. Numerous compensatory base pair changes have largely preserved same...