guanosine-triphosphate and Hypercholesterolemia

The characterisation of receptor sites of hormones to various tissues in vivo and in vitro have introduced new insights for the evaluation of pathogenic mechanisms involved in endocrine and metabolic human diseases. Disorders at the receptor level are characterized by changes in the number of receptor sites, the affinity of the hormone to its specific receptors or by generation of anti-receptor antibodies, which impair hormone binding procedures or post-receptor metabolism. Altered receptor physiology may be of an important value as well for diagnosis and treatment of endocrine, metabolic and neoplastic diseases as for the understanding of their pathogenetic mechanisms.

Topics: Acanthosis Nigricans; Adenosine Triphosphate; Adenylyl Cyclases; Antibodies; Binding, Competitive; Cyclic AMP; Diabetes Complications; Endocrine System Diseases; Enzyme Activation; Graves Disease; Guanosine Triphosphate; Humans; Hypercholesterolemia; Insulin; Insulin Resistance; Lipoproteins, LDL; Metabolic Diseases; Myasthenia Gravis; Obesity; Receptors, Androgen; Receptors, Cell Surface; Receptors, Neurotransmitter

To identify genes responding to the cholesterol-rich diet, differentially expressed hepatic genes have been searched from a diet-induced hypercholesterolemic rabbit by differential display reverse transcription-polymerase chain reaction (DDRT-PCR). Among the many screened genes, Rab7 gene was shown to be distinctively up-regulated in response to the cholesterol-loading into the rabbit. To visualize the location of elevated Rab7 expression in tissues, patterns of the gene expression were monitored within hepatic and aortic tissues by in situ hybridization and immunohistochemistry. The expression of Rab7 was obviously increased in the hepatic tissues, especially in the endothelial cells and hepatocytes around central veins of the high cholesterol-fed rabbit, compared to the tissues from rabbit fed a normal diet. To find out a potential relationship between the Rab7 and the atherogenesis, the same experiments were conducted with the atherosclerotic plaques obtained from rabbit and human. The elevated expression of Rab7 gene was clearly evident in both tissues, suggesting that the Rab7 may be involved in the process of atherogenesis.

Topics: Amino Acid Sequence; Animals; Aorta; Binding Sites; Cholesterol, Dietary; Dogs; Gene Expression Regulation; Guanosine Triphosphate; Humans; Hypercholesterolemia; Liver; Male; Molecular Sequence Data; Muscle, Smooth, Vascular; rab GTP-Binding Proteins; rab7 GTP-Binding Proteins; Rabbits; Rats; Reverse Transcriptase Polymerase Chain Reaction; Sequence Alignment; Sequence Homology, Amino Acid