Sampangine Inhibits Heme Biosynthesis in both Yeast and Human
| Autor: | Xuewen Pan, Yongxiang Li, Ameeta K. Agarwal, Tao Xu, Zhiwei Huang, John D. Phillips, Kaifu Chen, Wei Li, Alice M. Clark, Jianhuai Zhang |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Uroporphyrinogens Saccharomyces cerevisiae Heme Heterocyclic Compounds 4 or More Rings Microbiology Mitochondrial Proteins Jurkat Cells chemistry.chemical_compound Alkaloids ATP-Dependent Proteases Uroporphyrinogen Cell Line Tumor medicine Humans Protoporphyrinogen Oxidase Naphthyridines Molecular Biology Cell Proliferation chemistry.chemical_classification Reactive oxygen species biology Plant Extracts Articles General Medicine Mitochondrial Proton-Translocating ATPases biology.organism_classification Uroporphyrinogen III Synthetase Electron transport chain Yeast Mechanism of action chemistry Biochemistry medicine.symptom Reactive Oxygen Species |
| Zdroj: | Eukaryotic Cell. 10:1536-1544 |
| ISSN: | 1535-9786 1535-9778 |
| DOI: | 10.1128/ec.05170-11 |
| Popis: | The azaoxoaporphine alkaloid sampangine exhibits strong antiproliferation activity in various organisms. Previous studies suggested that it somehow affects heme metabolism and stimulates production of reactive oxygen species (ROS). In this study, we show that inhibition of heme biosynthesis is the primary mechanism of action by sampangine and that increases in the levels of reactive oxygen species are secondary to heme deficiency. We directly demonstrate that sampangine inhibits heme synthesis in the yeast Saccharomyces cerevisiae . It also causes accumulation of uroporphyrinogen and its decarboxylated derivatives, intermediate products of the heme biosynthesis pathway. Our results also suggest that sampangine likely works through an unusual mechanism—by hyperactivating uroporhyrinogen III synthase—to inhibit heme biosynthesis. We also show that the inhibitory effect of sampangine on heme synthesis is conserved in human cells. This study also reveals a surprising essential role for the interaction between the mitochondrial ATP synthase and the electron transport chain. |
| Databáze: | OpenAIRE |
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