RRC ID 10893
著者 Hoshino K, Momiyama E, Yoshida K, Nishimura K, Sakai S, Toida T, Kashiwagi K, Igarashi K.
タイトル Polyamine transport by mammalian cells and mitochondria: role of antizyme and glycosaminoglycans.
ジャーナル J Biol Chem
Abstract The role of antizyme (AZ) and glycosaminoglycans in polyamine uptake by mammalian cells and mitochondria was examined using NIH3T3 and FM3A cells and rat liver mitochondria. AZ is synthesized as two isoforms (29 and 24.5 kDa) due to the existence of two initiation codon AUGs in the AZ mRNA. Most AZ existed as the 24.5-kDa form translatable from the second AUG, but a portion of the 29-kDa AZ from the first AUG was associated with mitochondria because of the presence of a mitochondrial targeting signal between the first and the second methionine. The predominance of the 24.5-kDa isoform was mainly due to the presence of spermidine and a favorable sequence context (Kozak sequence) at the second initiation codon AUG. Spermine uptake by NIH3T3 cells was inhibited by both 29- and 24.5-kDa AZs, but uptake by rat liver mitochondria was not influenced by either form of AZ. Because spermine uptake by mitochondria caused a release of cytochrome c, an enhancer of apoptosis, we looked for inhibitors of mitochondrial spermine uptake other than AZ. Cations such as Na+, K+, and Mg2+ were inhibitors of the mitochondrial uptake. It has been reported that heparan sulfate on glypican-1 plays important roles in spermine uptake by human embryonic lung fibroblasts. Heparin, but not heparan sulfate, slightly inhibited spermine uptake by FM3A cells in the absence of Mg2+ and Ca2+ but had no effect under physiological conditions in the presence of Mg2+ and Ca2+.
巻・号 280(52)
ページ 42801-8
公開日 2005-12-30
DOI 10.1074/jbc.M505445200
PII S0021-9258(19)47888-5
PMID 16263714
MeSH Amino Acid Sequence Animals Blotting, Western Calcium / chemistry Cell Line Codon, Initiator Cytochromes c / metabolism Dose-Response Relationship, Drug Fibroblasts / metabolism Glycosaminoglycans / chemistry* Heparitin Sulfate / chemistry Humans Kinetics Liver / metabolism Lung / embryology Magnesium / chemistry Methionine / chemistry Mice Mitochondria / metabolism* Mitochondria, Liver / metabolism Models, Chemical Molecular Sequence Data Mutagenesis, Site-Directed NIH 3T3 Cells Plasmids / metabolism Polyamines / metabolism* Protein Isoforms Protein Structure, Tertiary Proteins / chemistry* RNA, Messenger / metabolism Rats Spermine / metabolism Spermine / pharmacokinetics Time Factors Transfection
IF 4.238
引用数 34
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 WI-38(RCB0704)