Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The insulin-like growth factor I receptor (IGF-I-R) gene is expressed in most body tissues. The levels of IGF-I-R mRNA, however, are regulated by a number of physiological conditions (development, differentiation, and hormonal milieu) as well as in certain pathological states (diabetes and tumors). To understand the molecular mechanisms which control the transcription of the IGF-I-R gene, we have cloned the promoter of the rat receptor gene and have characterized its activity by transient expression assays. Different fragments of the 5'-flanking region (subcloned upstream of a luciferase reporter gene) were transfected into buffalo rat liver 3A cells (a cell line with a low number of IGF-I binding sites) and Chinese hamster ovary cells (a cell line with a higher number of cell-surface receptors). In both cell lines, most of the promoter activity was located in the proximal 416 base pairs of 5'-flanking region. However, further dissection of this proximal fragment revealed a cell type-specific pattern of promoter activity. Thus, in buffalo rat liver 3A cells, subfragments of this region each contributed to total activity, suggesting that contiguous cis-elements can act together to activate transcription. In Chinese hamster ovary cells, on the other hand, subfragments of the proximal promoter region partially substituted for the proximal 416 base pairs of 5'-flanking region. Coexpression studies using an IGF-I-R promoter reporter construct together with an Sp1 expression vector (under the control of an ADH promoter) were performed in SL2 cells, a Drosophila cell line which lacks endogenous Sp1. The results obtained showed that Sp1 can trans-activate the IGF-I-R promoter in vivo. Transient transfection assays were complemented with gel-retardation assays and DNase I footprinting experiments, which showed that transcription factor Sp1 is potentially an important regulator of IGF-I-R gene expression.
 ...
PMID:Structural and functional analysis of the insulin-like growth factor I receptor gene promoter. 144 10

The effect of insulin-like growth factor I (IGF-I) on the activity of alcohol dehydrogenase was determined in primary hepatocyte culture from male rats. Continuous exposure of hepatocytes to IGF-I (30 nM) resulted in increases in alcohol dehydrogenase activity on Days 3-6 of culture. The increase in enzyme activity was preceded by increased alcohol dehydrogenase mRNA, indicating that the effect of IGF-I was at the pretranslational level. The effect of IGF-I was observed only in the presence of pharmacological concentrations of insulin in the media. Insulin alone had no effect on alcohol dehydrogenase activity. The permissive influence of insulin was correlated with the ability of insulin to maintain a steady high number of IGF-I binding receptors in the hepatocytes during culture. The response of alcohol dehydrogenase to IGF-I is similar to that previously demonstrated for growth hormone and suggests the possibility that the effect of growth hormone on this enzyme may be mediated by IGF-I.
 ...
PMID:Effect of insulin-like growth factor I on rat alcohol dehydrogenase in primary hepatocyte culture. 216 56

Aging is a complex biological process with contributions from a wide variety of genes including insulin-like growth factor I and alcohol dehydrogenase (ADH), which decline with advanced age. The goal of this study was to examine if ADH enzyme plays any role in cardiac aging. Ventricular myocytes were isolated from young (2-3 months old) or aged (26-28 months old) male FVB wild-type and cardiac-specific ADH (class I, isozyme type 1) transgenic mice. Mechanical properties were measured using an IonOptix system. Aged FVB myocytes displayed significantly reduced ADH activity compared with young ones, which was restored by the ADH transgene. Compared with young cardiomyocytes, aged FVB myocytes exhibited prolonged relengthening duration and a steaper decline in peak shortening amplitude in response to elevated electrical stimuli. Although ADH transgene itself did not alter mechanical properties in young mice, it rescued aging-associated diastolic dysfunction without affecting dampened contractile response to high stimulus frequency. Immunoblot analysis revealed reduced sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) and Na(+)-Ca(2+) exchanger (NCX) levels in conjunction with enhanced phospholamban expression in aged FVB hearts. ADH transgene prevented aging-induced reduction in SERCA2a and NCX without affecting up-regulated phospholamban. Our data suggest that aging is associated with a reduced ADH enzymatic activity and diastolic dysfunction, which may be corrected with cardiac overexpression of the ADH enzyme. Alteration in cardiac Ca(2+) cycling proteins including SERCA2a and NCX may play a role in both pathogenesis of cardiac aging and the beneficial effect of ADH enzyme.
 ...
PMID:Cardiac overexpression of alcohol dehydrogenase (ADH) alleviates aging-associated cardiomyocyte contractile dysfunction: role of intracellular Ca2+ cycling proteins. 1684 98