1989 Fiscal Year Final Research Report Summary
Physiological role of neonatal brain-derived carcinostatic factor(NBCF) during the ontogenesis
| Project/Area Number |
62571003
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Hiroshima Prefectural University (1989)
国立予防衛生研究所 (1987-1988) |
|---|
Principal Investigator |
MIWA Nobuhiko Hiroshima Prefectural University, Faculty of Bio-Resources, Assistant Professor, 生物資源学部・生物工学講座, 助教授 (00142141)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Satoshi National Institute of Health, Department of Antibiotics, Chief of Department, 抗生物質部, 部長 (60072930)
MATSUNO Tetsuya National Institute of Health, Department of Mearsles Virus, Chief of Laboratory, 麻疹ウイルス部, 室長 (30109970)
|
|---|
| Project Period (FY) |
1987 – 1989
|
| Keywords | THE NERVOUS SYSTEM / ONTOGENESIS / PROGRAMMED CELL DEATH / ANTITUMOR FACTOR / NEUROBLASTOMA / GLUTAMINE METABOLISM / INDUCTION OF DIFFERENTIATION |
|---|
| Research Abstract |
The mouse brain, at the neonatal stage but not at the adult or fetal stage, secretes a protein, which inhibits growth and DNA synthesis of malignant cells preferentially over those of normal cells, and so is termed neonatal brain-derived carcino- static factor (NBCF). In the present study NBCF was prepared from conditioned medium of the neonatal brain cultured, and was obtained by HPLC as a homogeneous protein (62 kDa, PI 9.1); physics-chemical and biological properties of NBCF differ from those of cerebral proteins known. A 1,2-cis-diol affinity column retained NBCF, which was thereafter eluted with D-sorbitol; NBCF treated with neuraminidase lost part of activity without emergence of new N-terminal amino acids, suggesting glycan moieties required for the activity exhibition. This is supported by repression of NBCF secretion by tunicamycin of doses as low as is not cytotoxic. NBCF did not hydrolize target proteins; cytotoxic action of NBCF was not counteracted by a diversity of protease inhibitors. An ether-extract of NBCF was not cytotoxic whereas the ether-insoluble residuum retained part of the initial activity. NBCF was inactivated with immobilized trypsin or with dithiothreitol combined with guanidine more markedly than with either agent. Thus cytotoxicity exhibition of NBCF, mediated through actions other than proteolysis, is attributed to the proteinic principle but not to protein-bound lipophilic ligands, and requires retention of the protein conformation and intramolecularly buried SS bonds.
|
