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Gizatullina 2011 Mitochondrion

From Bioblast
Publications in the MiPMap
Gizatullina ZZ, Gaynutdinov TM, Svoboda H, Jerzembek D, Knabe A, Vielhaber S, Malesevic M, Heinze HJ, Fischer G, Striggow F, Gellerich FN (2011) Effects of cyclosporine A and its immunosuppressive or non-immunosuppressive derivatives [D-Ser]8-CsA and Cs9 on mitochondria from different brain regions. Mitochondrion 11(3):421-9.

» PMID: 21167961

Gizatullina ZZ, Gaynutdinov TM, Svoboda H, Jerzembek D, Knabe A, Vielhaber S, Malesevic M, Heinze HJ, Fischer G, Striggow F, Gellerich FN (2011) Mitochondrion

Abstract: We studied the functional properties of isolated brain mitochondria (BM) prepared from total rat brain (BM(total)) or from cerebral subregions under basal and Ca(2+) overload conditions in order to evaluate the effects of cyclosporine A (CsA) in a regiospecific manner. CsA-induced effects were compared with those of two derivatives-the none-immunosuppressive [O-(NH(2)(CH2)(5)NHC(O)CH(2))-D-Ser](8)-CsA (Cs9) and its congener, the immunosuppressive [D-Ser](8)-CsA. The glutamate/malate-dependent state 3 respiration of mitochondria (state 3(glu/mal)) differed in region-specific manner (cortex > striatum = cerebellum > substantia nigra > hippocampus), but was significantly increased by 1μM CsA (+21±5%) in all regions. Ca(2+) overload induced by addition of 20μM Ca(2+) caused a significant decrease of state 3(glu/mal) (-45 to -55%) which was almost completely prevented in the presence of 1μM CsA, 1μM Cs9 or 1μM [D-Ser](8)-CsA. Mitochondrial Ca(2+) accumulation thresholds linked to permeability transition (PT) as well as the rate and completeness of mitochondrial Ca(2+) accumulation differed between different brain regions. For the first time, we provide a detailed, regiospecific analysis of Ca(2+)-dependent properties of brain mitochondria. Regardless of their immunosuppressive impact, CsA and its analogues improved mitochondrial functional properties under control conditions. They also preserved brain mitochondria against Ca(2+) overload-mediated PT and functional impairments. Since Cs9 does not mediate immunosuppression, it might be used as a more specific PT inhibitor than CsA. Keywords: Mitochondria, Cortex, Cerebellum, Striatum, Hippocampus, Substantia nigra, Cyclosporine A, CsA derivatives, Energy metabolism, Permeability transition pore

O2k-Network Lab: DE Magdeburg Gellerich FN


Labels: MiParea: Respiration 

Stress:Permeability transition  Organism: Rat  Tissue;cell: Nervous system  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS  Pathway: N, S  HRR: Oxygraph-2k