tailieunhanh - Báo cáo khoa học: Impairment of mitochondrial function by minocycline

There is an ongoing debate on the presence of beneficial effects of mino-cycline (MC), a tetracycline-like antibiotic, on the preservation of mito-chondrial functions under conditions promoting mitochondria-mediated apoptosis. | ỊFEBS Journal Impairment of mitochondrial function by minocycline I flfl n 11 nep K1 2 QI i a I ar a 3 Pp pt it7man n1 2 XA olf2 laiiQ-XA ornoi XA allocnK3 aieei I upsc via die eiei leutzmaHH eia o aus eii lei aeoc Detlef Siemen3 and Peter Scheinfeld1 1 Institute of Biochemistry and CellBiology Otto-von-Guericke University Magdeburg Germany 2 Institute of MedicalNeurobiology Otto-von-Guericke University Magdeburg Germany 3 Department of Neurology Otto-von-Guericke University Magdeburg Germany Keywords magnesium minocycline mitochondria neuroprotection permeability transition Correspondence K. Kupsch Institute of Biochemistry and CellBiology Otto-von-Guericke University Magdeburg Leipziger Str. 44 D-39120 Magdeburg Germany Fax 49 391 6714365 Tel 49 391 6714362 E-mail kkupsch@ These authors contributed equally to this work Received 7 November 2008 revised 8 January 2009 accepted 13 January 2009 doi There is an ongoing debate on the presence of beneficial effects of minocycline MC a tetracycline-like antibiotic on the preservation of mitochondrial functions under conditions promoting mitochondria-mediated apoptosis. Here we present a multiparameter study on the effects of MC on isolated rat liver mitochondria RLM suspended either in a KCl-based or in a sucrose-based medium. We found that the incubation medium used strongly affects the response of RLM to MC. In KCl-based medium but not in sucrose-based medium MC triggered mitochondrial swelling and cytochrome c release. MC-dependent swelling was associated with mitochondrial depolarization and a decrease in state 3 as well as uncoupled respiration. Swelling of RLM in KCl-based medium indicates that MC per-meabilizes the inner mitochondrial membrane IMM to K and Cl . This view is supported by our findings that MC-induced swelling in the KCl-based medium was partly suppressed by N N -dicyclohexylcarbodiimide an inhibitor of IMM-linked K -transport and tributyltin an inhibitor of the