Prohibitin is an evolutionarily conserved gene with homologues found in organisms ranging from yeast to man. In man the gene is located on chromosome 17 at q21. The deduced amino acid sequences of the protein products from mouse and rat are identical; and these differ from the human protein sequence by a single conserved amino acid. Prohibitin has antiproliferative activity and available data suggest a role in such diverse processes as normal cell cycle regulation, replicative senescence, cellular immortalization, and the development of sporadic breast tumors. Although its functional activity is presently unknown, the 30,000-Da protein has been located in the inner membrane of mitochondria, where it is postsynthetically modified, as well as on the plasma membrane of B cells, where it is associated with the IgM receptor. Prohibitin's evolutionary conservation and ubiquitous expression indicate that it is a fundamentally important gene; and current data suggest a functional role in such dissimilar processes as development, senescence, and tumor suppression.

Aging↗

PubMedDate not supplied

Prohibitin and the senescent phenotype.

Prohibitin is an evolutionarily conserved gene that has antiproliferative activity, is ubiquitously expressed, and appears to be essential for cell survival. The gene codes for a 30 kD, post-synthetically modified protein located primarily in the mitochondria. It functionally inhibits cell cycle traverse and DNA synthesis, but its mechanism of action is presently unknown. Prohibitin is proposed to be a member of a new class of tumor suppressor genes whose inhibitory activity plays a role in the dominant senescent phenotype. Its involvement in senescence has been postulated from results obtained from such diverse systems as yeast and human diploid fibroblasts. Additional data show that prohibitin is involved in one of the limited number of pathways that results in the loss of the senescent phenotype and leads to cellular immortalization. Its involvement, however, occurs downstream in the pathway and is postulated to be part of the lost tumor suppressor activities associated with tumorigenicity.

Animals↗

PubMedDate not supplied

Effect of tauroursodeoxycholic acid (TUDCA) on biliary lipid composition.

TUDCA has been proposed in the treatment of hepatobiliary disease, but data on the enrichment of the biliary TUDCA pool and changes of biliary lipids after administration of the compound are scarce. We studied the composition of biliary lipids in a series of 33 patients with radiolucent stones, before and after treatment with TUDCA, 3.5 to 16.6 mg/kg/die for 4-6 weeks. Duodenal bile was collected with the Entero-Test after gallbladder contraction. Cholesterol saturation was 147% + 67 before treatment. TUDCA administration produced the following dose-dependent effects: a) a linear decrease of cholesterol saturation (r = 0.59; p); b) a non-linear increase of the percent of ursodeoxycholate in bile (r = 0.59; p); c) a non-linear increase of the fraction of ursodeoxycholate conjugated with taurine. At the dose of 11 mg/kg per day, cholesterol saturation was 80%, ursodeoxycholic acid represented about 45% of biliary bile acids, and about half of urso was conjugated with taurine. These results can be used as guidelines to assess the required daily dosage of TUDCA.

Adult↗

PubMedDate not supplied

Effects of thyroid status on cold-adaptive thermogenesis in Brandt's vole, Microtus brandti.

Hyper- and hypothyroidism were induced by subcutaneous injection of thyroxine and by oral administration of methimazol in Brandt's voles. The effects of the two treatments on metabolic thermogenesis at 25 degrees C and 4 degrees C were investigated. The level of resting metabolic rate was closely related to thyroid status: high in the hyperthyroid case and low in the hypothyroid case. However, no increase in resting metabolic rate occurred in either case during further cold acclimation. Hyperthyroidism resulted in an increased nonshivering thermogenesis, which was much enhanced by lower temperature, but hypothyroidism led to a suppressed nonshivering thermogenesis in the cold. The state-4 and state-3 respirations and the activities of cytochrome-c oxidase of liver mitochondria were elevated in hyperthyroid animals but attenuated in hypothyroid ones. However, these levels were scarcely changed after further cold acclimation. Both hyperthyroidism and cold acclimation induced the recruitment of brown adipose tissue, but brown adipose tissue was different biochemically in the two cases: in hyperthyroidism, the total protein was reduced, while fat content increased; in cold acclimation, the total and mitochondrial proteins were increased. However, in hypothyroid voles, the normal adaptive changes in brown adipose tissue were impaired in further cold acclimation. The activity of cytochromec oxidase in brown adipose tissue was increased by hyperthyroidism and enhanced in further cold. In contrast, its activity was inhibited in hypothyroid animals, though activated to some extent in cold. These results demonstrate that normal thyroid function is essential for the cold-induced increase of resting metabolic rate and nonshivering thermogenesis and that there is a synergism between thyroid hormone and cold acclimation in the regulation of nonshivering thermogenesis in Brandt's vole. In addition, the blunted response of brown adipocytes to the cold may be the cytological mechanism for the suppressed nonshivering thermogenesis found with hypothyroidism.

Adaptation, Physiological↗