Molecular basis for the actions of Hsp90 inhibitors and cancer therapy.

Heat-shock protein 90 (Hsp90) inhibitor downregulates c-Myc expression and upregulates the expression of tumor repressor proteins such as p53 and pRB, inhibiting the G1/S transition and causing G2/M arrest during cell cycle progression. The cycle progression is extensively controlled by the pRB/E2F signaling pathway. E2F is released from the pRB/E2F complex with the phosphorylation of pRB by cyclin-cyclin-dependent kinase (CDK) complexes.

Genetic analysis of hepatitis C virus with defective genome and its infectivity in vitro.

Replication and infectivity of hepatitis C virus (HCV) with a defective genome is ambiguous. We molecularly cloned 38 HCV isolates with defective genomes from 18 patient sera. The structural regions were widely deleted, with the 5' untranslated, core, and NS3-NS5B regions preserved.

Inhibitory effect of Yunnan traditional medicines on hepatitis C viral polymerase.

For the purpose of developing novel anti-hepatitis C virus (HCV) agents from natural resources, 93 Yunnan crude drugs were screened for their inhibitory effects on RNA-dependent RNA polymerase (RdRp) of HCV. Although 71 methanol extracts and 50 water extracts inhibited HCV-RdRp by more than 50% at a concentration of 50 μg/ml, the majority of them contained a high percentage of tannins. However, methanol extracts of Plumbago zeylanica (branch), Maytenus fookerii (leaf) and Huashidancha (Y61, branch and leaf), and water extracts of Potentilla griffithii (whole plant) and Salvia yunnanensis (underground part), having IC values of less than 10 μg/ml, showed less than 10% tannin content.

Continuous depolarization induces choline acetyltransferase activity in septal and hippocampal co-cultured embryonic rat neurons.

We tested the influence of continuous high-K+ treatment on acetylcholine (ACh) release and choline acetyltransferase (ChAT) activity on septal cell culture, and septal and hippocampal cell co-culture obtained from rat embryos. Continuous 9 mM K+ treatment did not affect ACh release and ChAT activity in septal culture, but increased ACh release in co-culture without affecting ChAT activity. A slight increase in extracellular K+ concentration, therefore, induced neuronal excitation.

Human immunodeficiency virus-reverse transcriptase inhibition and hepatitis C virus RNA-dependent RNA polymerase inhibition activities of fullerene derivatives.

We examined the human immunodeficiency virus-reverse transcriptase and hepatitis C virus RNA-dependent RNA polymerase inhibition activities of cationic, anionic, and amino acid-type fullerene derivatives. Among the fullerene derivatives, the amino acid-type fullerene derivative was the most efficient in human immunodeficiency virus-reverse transcriptase inhibition.

Molecular cloning of the gene for edeine B1 amidinohydrolase in addition to the agmatinase activity in Bacillus subtilis.

A gene with a high-nucleotide sequence homology to the edeine B1 amidinohydrolase gene of Bacillus brevis was identified in the database of the Bacillus subtilis genome. The gene was isolated, expressed in Escherichia coli, and the gene product was analyzed with regard to the characteristics of its enzyme activity. A 32-kDa protein encoded by the ywhG gene showed a 69.

Gerbils of a seizure-sensitive strain have a mitochondrial inner membrane protein with different isoelectric points from those of a seizure-resistant strain.

The distribution of proteins in the cerebral cortex of a seizure-sensitive (SS) strain of gerbil and its seizure-resistant (SR) counterpart was profiled using two-dimensional gel electrophoresis. A series of proteins of similar molecular weight (around 83 kDa) showed small but consistent differences in their isoelectric point (pI) with indistinguishable profiles of distribution between the two strains. Amino acid sequences of peptides produced by limited proteolysis of each protein in the spots from the strains were identical or highly homologous to those of mitofilin, a mitochondrial inner membrane protein (IMMT) in humans.