New Mechanism for Release of Endosomal Contents: Osmotic Lysis via Nigericin-Mediated K+/H+ Exchange
| Autor: | Ananda Kumar Kanduluru, Andrea L. Kasinski, Fei You, Esteban A. Orellana, N. Achini Bandara, Madduri Srinivasarao, Philip S. Low, Loganathan Rangasamy, Venkatesh Chelvam |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pharmacology Nigericin Endosome Organic Chemistry Biomedical Engineering Pharmaceutical Science Bioengineering Endocytosis 03 medical and health sciences chemistry.chemical_compound Cytolysis Cytosol 030104 developmental biology 0302 clinical medicine chemistry Cytoplasm 030220 oncology & carcinogenesis Extracellular Biophysics Intracellular Biotechnology |
| Zdroj: | Bioconjugate Chemistry. 29:1047-1059 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/acs.bioconjchem.7b00714 |
| Popis: | Although peptides, antibodies/antibody fragments, siRNAs, antisense DNAs, enzymes, and aptamers are all under development as possible therapeutic agents, the breadth of their applications has been severely compromised by their inability to reach intracellular targets. Thus, while macromolecules can often enter cells by receptor-mediated endocytosis, their missions frequently fail due to an inability to escape their entrapping endosomes. In this paper, we describe a general method for promoting release of any biologic material from any entrapping endosome. The strategy relies on the fact that all nascent endosomes contain extracellular (Na+-enriched) medium, but are surrounded by intracellular (K+-enriched) fluid in the cytoplasm. Osmotic swelling and rupture of endosomes will therefore be facilitated if the flow of K+ down its concentration gradient from the cytosol into the endosome can be facilitated without allowing downhill flow of Na+ from the endosome into the cytosol. While any K+ selective ionopho... |
| Databáze: | OpenAIRE |
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