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@ARTICLE{Gizatullina:136212,
author = {Gizatullina, Zemfira Z and Gaynutdinov, Timur M and
Svoboda, Hanno and Jerzembek, Doreen and Knabe, Annette and
Vielhaber, Stefan and Malesevic, Miroslav and Heinze,
Hans-Jochen and Fischer, Gunter and Striggow, Frank and
Gellerich, Frank N},
title = {{E}ffects of cyclosporine {A} and its immunosuppressive or
non-immunosuppressive derivatives [{D}-{S}er]8-{C}s{A} and
{C}s9 on mitochondria from different brain regions.},
journal = {Mitochondrion},
volume = {11},
number = {3},
issn = {1567-7249},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DZNE-2020-02534},
pages = {421-429},
year = {2011},
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 = {Animals / Brain: drug effects / Calcium: metabolism / Cell
Respiration: drug effects / Cyclosporine: metabolism /
Energy Metabolism: drug effects / Enzyme Inhibitors:
metabolism / Male / Mitochondria: drug effects / Rats /
Enzyme Inhibitors (NLM Chemicals) / Cyclosporine (NLM
Chemicals) / Calcium (NLM Chemicals)},
cin = {U Clinical Researchers - Magdeburg / AG Striggow},
ddc = {540},
cid = {I:(DE-2719)7000000 / I:(DE-2719)5000045},
pnm = {344 - Clinical and Health Care Research (POF3-344) / 342 -
Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-344 / G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:21167961},
doi = {10.1016/j.mito.2010.12.012},
url = {https://pub.dzne.de/record/136212},
}