GSTΠ stimulates caveolin-1-regulated polyamine uptake via actin remodeling.
| Autor: | Uemura T; Amine Pharma Research Institute, Chuo-ku, Chiba 260-0856, Japan., Tsaprailis G; Center for Toxicology, College of Pharmacy, Tucson, Arizona 85721, USA., Gerner EW; Cancer Prevention Pharmaceuticals, Tucson, Arizona 85718, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Oncotarget [Oncotarget] 2019 Oct 01; Vol. 10 (55), pp. 5713-5723. Date of Electronic Publication: 2019 Oct 01 (Print Publication: 2019). |
| DOI: | 10.18632/oncotarget.27192 |
| Abstrakt: | Polyamines spermidine and spermine, and their diamine precursor putrescine, are essential for normal cellular functions in both pro- and eukaryotes. Cellular polyamine levels are regulated by biosynthesis, degradation and transport. Transport of dietary and luminal bacterial polyamines in gastrointestinal (GI) tissues plays a significant role in tissue polyamine homeostasis. We have reported that caveolin-1 play an inhibitory role in polyamine uptake in GI tissues. We investigated the mechanism of caveolin-1-regulated polyamine transport. We found that glutathione S -transferase Π(GSTΠ) was secreted from caveolin-1 knockdown cells and stimulated spermidine transport in human colon-derived HCT116 cells. GSTΠ secreted in the medium increased S -glutathionylated protein level in the plasma membrane fraction. Proteomic analysis revealed that actin was S -glutathionylated by GSTΠ. Immunofluorescence microscopy demonstrated that actin filaments around plasma membrane were S -glutathionylated in caveolin-1 knockdown cells. Inhibition of actin remodeling by jasplakinolide caused a decrease in polyamine uptake activity. These data support a model in which caveolin-1 negatively regulates polyamine uptake by inhibiting GSTΠ secretion, which stimulates actin remodeling and endocytosis. Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests. (Copyright: © 2019 Uemura et al.) |
| Databáze: | MEDLINE |
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