Abstract
Available data indicate that minocycline, an antibiotic of the tetracycline family, has cytoprotective properties due to a direct interaction with mitochondria. Yet, the data in the case of isolated mitochondria suggest discrepant or even detrimental effect(s) of the interaction. We have studied the cytoprotective activity displayed by minocycline in the case of the yeast Saccharomyces cerevisiae cells pretreated with H₂O₂. We demonstrated that the activity of minocycline required the presence of VDAC (voltage-dependent anion-selective channel) and provided distinct improvement of mitochondrial coupling. In the case of isolated mitochondria, we verified that minocycline exhibited uncoupler activity when applied in micromolar concentrations. However, when added in nanomolar concentrations, minocycline was able to improve the level of coupling for isolated mitochondria. The coupling improvement effect was observed in mitochondria containing VDAC but not in Δpor1 mitochondria (depleted of VDAC1, termed here VDAC) and in both types of mitoplasts. Thus, properly low concentrations of minocycline within the cell in the vicinity of VDAC-containing mitochondria enable the improvement of energy coupling of mitochondria that contributes to cytoprotective activity of minocycline.
Highlights
Minocycline, a derivative of tetracycline (7-dimethylamino6-dimethyl-6-deoxytetracycline), is an antibiotic displaying broad-spectrum antibacterial activity and commonly indicated in the treatment of diseases with an inflammatory background (e.g. Vandekerckhove et al 1998)
We have reported recently that VDAC1 is important for cytoprotective activity of minocycline observed for exponentially growing S. cerevisiae cells exposed to H2O2 (Gałgańska et al 2010)
Since voltage-dependent anion-selective channel (VDAC) is a mitochondrial protein and mitochondria are regarded as a target of minocycline cytoprotective capability, we decided to further examine the rate of respiration in wild type and Δpor1 cells under the studied conditions
Summary
Minocycline, a derivative of tetracycline (7-dimethylamino6-dimethyl-6-deoxytetracycline), is an antibiotic displaying broad-spectrum antibacterial activity and commonly indicated in the treatment of diseases with an inflammatory background (e.g. Vandekerckhove et al 1998). On the other hand, increasing data point toward cytoprotective properties of minocycline and its potential use in the treatment of different diseases. There are more than 300 publications on minocycline-induced neuroprotection, including experimental models of human diseases and clinical trials (reviewed in, e.g. Kim and Suh 2009; Plane et al 2010). It is concluded that the cytoprotective capability of minocycline results from its anti-inflammatory, anti-apoptotic, and antioxidant properties (e.g. Jordan et al 2007; Plane et al 2010). A detailed description of cellular and molecular mechanism(s) triggered by minocycline appears to be current and important
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