Increased assembly of cytoskeletal proteins associated with the transformation of human liver cells into fibroblast-like cells.

A topoisomerase II inhibitor, novobiocin, and a deacetylase inhibitor, butyrate, synergistically transformed human liver cells into fibroblast-like cells. This morphological change was associated with an increased production of procollagen type III peptide and a simultaneous assembly of actin, tubulin, vimentin and cytokeratin. Novobiocin and butyrate had no marked effect on the phosphorylation state of cytokeratin proteins, but synergistically enhanced [3H]acetate uptake. From these results, it can be speculated that protein acetylation plays an important role in inducing the assembly of cytoskeletal proteins and the morphological transformation of human liver cells.     

Hypothalamic histamine modulates adaptive behavior of rats at high environmental temperature

Summary Histamine content in the rat hypothalamus was lower at 4°C and higher at 31°C compared to that at 21°C. Pretreatment with -fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase, attenuated both the increased level of hypothalamic histamine and rat adaptive behavior at 31°C. Increase of histamine content in the hypothalamus appears to be an important factor contributing to rat adaptive behavior to high environmental temperature.     

Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor

Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach.     

Inhibitory effect of cytokinins on PHA-induced human lymphocyte stimulation

Summary The inhibitory effect of various purine derivatives on PHA-induced human lymphocyte blast formation was studied. Two nucleoside cytokinins, N⁶-benzyladenosine and N⁶-isopentenyladenosine, inhibited blast formation at concentrations as low as 10^–6 M. However, the other cytokinins, which lacked the ribosyl residue at N⁹ position, had to be at the higher molar concentration of 10^–4 before they could induce the same inhibitory effect.     

Development of adenocarcinomas after transplantation of rat glandular stomachs treated in vitro with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)

Cellular and Molecular Life Sciences - Glandular stomachs of fetal and newborn Wistar rats were transplanted s.c. after treatment in vitro with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) at...     

Alpha-amylase inhibitor increases plasma 3-hydroxybutyric acid in food-restricted rats

The effect on energy metabolism of delayed absorption of starch by inhibition of -amylase was examined by considering levels of plasma glucose and 3-hydroxybutyric acid (3-OHBA) in rats. Addition of -amylase inhibitor (AI) to a high starch diet delayed the plasma glucose response after feeding: peak plasma glucose levels in the control group occurred 15 min after feeding, whereas in the AI group this peak did not occur until 30 min after. The total plasma glucose response was not different between the two groups. Plasma 3-OHBA levels 1 day after food restriction increased approximately five-fold in both groups. After 3 days of food restriction, the AI group maintained the same level of plasma 3-OHBA as after 1 day of food restriction, while the control group showed significantly decreased levels of 3-OHBA. After 3 days of food restriction, plasma insulin levels were significantly decreased in the AI group compared with the corresponding levels of the control group and with levels before the restriction. There was no significant difference in body weight between the two groups. These findings suggest that delayed hyperglycemia due to delayed absorption of starch following AI loading may attenuate insulin secretion, leading to altered metabolism of 3-OHBA during the delayed response to energy deficit.     

Structural view of cadherin-mediated cell-cell adhesion

Following the multiplication of biochemical, biophysical and structural studies describing cadherin molecules and their interactions, several ideas have emerged to explain the mechanisms of cadherin-mediated cell adhesion. Although different models were proposed for cadherin interactions, a consensus has come forth considering lateral dimerization of cadherins as being a central component of the cell-cell adhesion process. This review summarizes the recent development in structural studies of cadherins. Received 14 September 1998; received after revision 14 November 1998; accepted 16 November 1998     

Solubilization and characterization of a ouabain-sensitive protein from transverse tubule membrane-junctional sarcoplasmic reticulum complexes (TTM-JSR) in cat cardiac muscle

A new glycoprotein of 31,500 dalton, which has a high affinity for ouabain, and is independent of (Na+-K+)-ATPase, was solubilized from transverse tubule membrane and junctional sarcoplasmic reticulum complexes (TTM-JSR) of cat cardiac muscle. This protein could be extracted only in small amounts from sarcolemma-plasma membrane (SLM-PL) fragments, suggesting that it indeed originates from the TTM-JSR.