Biochemical and biophysical research communications, 2016-12, Vol.481 (1-2), p.117-124
2016
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- Autor(en) / Beteiligte
- Titel
- Lipophilic but not hydrophilic statin functionally inhibit volume-activated chloride channels by inhibiting NADPH oxidase in monocytes
- Ist Teil von
- Biochemical and biophysical research communications, 2016-12, Vol.481 (1-2), p.117-124
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Volume-activated Cl− channels (VACCs) can be activated by hypotonic solutions and have been identified in many cell types. Here, we investigated the effects of different statins on VACCs in monocytes. Whole-cell patch clamp recordings demonstrated that a hypotonic solution induced 5-nitro-2- (3-phenylpropylamino) benzoic acid (NPPB)- and 4,4′-diisothiocyanatostilbene-2, 2′-disulfonic acid (DIDS)-sensitive VACC currents in human peripheral monocytes and RAW 264.7 cells. The VACC currents were inhibited by the lipophilic statin (simvastatin) but not by the hydrophilic simvastatin acid and pravastatin. A low-molecular-weight superoxide anion scavenger (tiron, 1 mM) and inhibitor of NADPH oxidase (DPI 10 μM) was able to abolish the VACC currents. A hypotonic solution increased the reactive oxygen species (ROS) detected by the fluorescence of dichlorodihydrofluorescein (DCF), which was abolished by tiron and DPI. NPPB, DIDS, and simvastatin but not pravastatin decreased the fluorescence of DCF. Simvastatin could not further decrease VACC currents when pretreated with tiron or DPI, whereas exogenous H2O2 (100 μM), increased the VACC currents and overcame the blockade of VACC currents by simvastatin. Functionally, hypotonic solution increased the TNF-α mRNA expression, which could be decreased by tiron, DPI, NPPB, DIDS and simvastatin but not pravastatin. However, simvastatin could not decrease the TNF-α expression further when pretreatment with tiron, DPI, NPPB or DIDS. We conclude that lipophilic (simvastatin) rather than hydrophilic statin inhibit VACCs and decrease hyposmolality induced inflammation in monocytes by inhibiting NADPH oxidase. •A hypotonic solution induces volume-activated Cl− channel currents in monocytes.•Simvastatin regulates volume-activated chloride channels by inhibiting NADPH oxidase.•Simvastatin decrease hyposmolality induced inflammation by inhibiting NADPH oxidase.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-291XeISSN: 1090-2104DOI: 10.1016/j.bbrc.2016.11.007Titel-ID: cdi_proquest_miscellaneous_1837031101
- Format
- –
- Schlagworte
- Animals, Cells, Cultured, Chloride Channels - drug effects, Chloride Channels - physiology, Dose-Response Relationship, Drug, Humans, Hydrophobic and Hydrophilic Interactions, Hydroxymethylglutaryl-CoA Reductase Inhibitors - chemistry, Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology, Hypotonic Solutions - chemistry, Inflammation, Ion Channel Gating - drug effects, Ion Channel Gating - physiology, Lipids - chemistry, Mice, Monocytes, Monocytes - drug effects, Monocytes - physiology, NADPH Oxidases - antagonists & inhibitors, NADPH Oxidases - metabolism, Osmotic Pressure, Pravastatin, RAW 264.7 Cells, Reactive oxygen species, Simvastatin, Simvastatin - chemistry, Simvastatin - pharmacology, Volume-activated chloride channel