Journal Article

DZNE-2020-02534

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Effects of cyclosporine A and its immunosuppressive or non-immunosuppressive derivatives [D-Ser]8-CsA and Cs9 on mitochondria from different brain regions.

Gizatullina, Z. Z. ; Gaynutdinov, T. M. ; Svoboda, H. ; Jerzembek, D. ; Knabe, A. ; Vielhaber, S. ; Malesevic, M. ; Heinze, H.-J.DZNE* ; Fischer, G. ; Striggow, F.DZNE* ; Gellerich, F. N. (Corresponding author)

2011
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.mito.2010.12.012

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.

Keyword(s): Animals (MeSH) ; Brain: drug effects (MeSH) ; Calcium: metabolism (MeSH) ; Cell Respiration: drug effects (MeSH) ; Cyclosporine: metabolism (MeSH) ; Energy Metabolism: drug effects (MeSH) ; Enzyme Inhibitors: metabolism (MeSH) ; Male (MeSH) ; Mitochondria: drug effects (MeSH) ; Rats (MeSH) ; Enzyme Inhibitors ; Cyclosporine ; Calcium

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Contributing Institute(s):

1. U Clinical Researchers - Magdeburg (U Clinical Researchers - Magdeburg)
2. Neurodegeneration and Intervention Strategies (AG Striggow)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)
2. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2011

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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