| RRC ID |
10893
|
| Author |
Hoshino K, Momiyama E, Yoshida K, Nishimura K, Sakai S, Toida T, Kashiwagi K, Igarashi K.
|
| Title |
Polyamine transport by mammalian cells and mitochondria: role of antizyme and glycosaminoglycans.
|
| Journal |
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+.
|
| Volume |
280(52)
|
| Pages |
42801-8
|
| Published |
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
|
| Times Cited |
34
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
WI-38(RCB0704) |
