Functional Characterization of Transmembrane Intracellular pH Regulators and Mechanism of Alcohol-induced Intracellular Acidosis in Human Umbilical Cord Blood Stem Cell–Like Cells
| Autor: | Chung-Yi Lee, Yi-Ting Tsai, Jah-Yao Liu, Chien-Sung Tsai, Shih-Hurng Loh, Wei-Hwa Chen, Ming-Hurng Chen, Chien-Chih Ou |
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| Rok vydání: | 2011 |
| Předmět: |
Sodium-Hydrogen Exchangers
Intracellular pH Intracellular Space Umbilical Cord Blood Stem Cell Antigens CD34 Alcohol Umbilical cord Antiporters chemistry.chemical_compound medicine Humans Cells Cultured Amitrole Alcohol dehydrogenase Fomepizole Pharmacology Dose-Response Relationship Drug Ethanol biology Sodium-Bicarbonate Symporters Stem Cells Hydrogen-Ion Concentration Catalase Fetal Blood Fluoresceins Transmembrane protein Cell biology medicine.anatomical_structure chemistry Symporter biology.protein Pyrazoles Acidosis Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of Cardiovascular Pharmacology. 58:589-601 |
| ISSN: | 0160-2446 |
| Popis: | Changing intracellular pH (pHi) exerts considerable influence on many cellular functions. Different pHi regulators, such as the Na-H exchanger (NHE), Na/(Equation is included in full-text article.)symporter, and Cl/OH exchanger (CHE), have been identified in mature mammalian cells. The aims of the present study were to investigate the physiological mechanisms of pHi recovery and to further explore the effects of alcohol on the pHi in human umbilical cord blood CD34 stem cell-like cells (HUCB-CD34STs). HUCB-CD34STs were loaded with the pH-sensitive dye, 2',7'-bis(2-carboxethyl)-5(6)-carboxyfluorescein, to examine pHi. In isolated HUCB-CD34STs, we found that (1) the resting pHi is 7.03 ± 0.02; (2) 2 Na-dependent acid extruders and a Cl-dependent acid loading carrier exist and are functional; (3) alcohol functions in a concentration-dependent manner to reduce pHi and increase NHE activity, but it does not affect CHE activity; and (4) fomepizole, a specific alcohol dehydrogenase inhibitor, does not change the intracellular acidosis and NHE activity-induced by alcohol, whereas 3-amino-1, 2,4-trizole, a specific catalase inhibitor, entirely abolishes these effects. In conclusion, we demonstrate that 2 acid extruders and 1 acid loader (most likely NHE, NBC, and CHE, respectively) functionally existed in HUCB-CD34STs. Additionally, the intracellular acidosis is mainly caused by catalase-mediated alcohol metabolites, which provoke the activity of NHE. |
| Databáze: | OpenAIRE |
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