Rosuvastatin induces delayed preconditioning against oxygen-glucose deprivation in cultured cortical neurons.
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Tartalom: http://ajpcell.physiology.org/content/296/1/C97
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published


Type = Article
Cím:
Rosuvastatin induces delayed preconditioning against oxygen-glucose deprivation in cultured cortical neurons.
Létrehozó:
Domoki, Ferenc
Kis, Béla
Gáspár, Tamás
Bari, Ferenc
Dátum:
2009
Téma:
QH301 Biology / biológia
QP Physiology / élettan
Tartalmi leírás:
We tested whether rosuvastatin (RST) protected against oxygen-glucose deprivation
(OGD)-induced cell death in primary rat cortical neuronal cultures. OGD reduced
neuronal viability (%naive controls, mean +/- SE, n = 24-96, P < 0.05) to 44 +/-
1%, but 3-day pretreatment with RST (5 microM) increased survival to 82 +/- 2% (P
< 0.05). One-day RST treatment was not protective. RST-induced neuroprotection
was abolished by mevalonate or geranylgeranyl pyrophosphate (GGPP), but not by
cholesterol coapplication. Furthermore, RST-induced decreases in neuronal
cholesterol levels were abolished by mevalonate but not by GGPP. Reactive oxygen
species (ROS) levels were reduced in RST-preconditioned neurons after OGD, and
this effect was also reversed by both mevalonate and GGPP. These data suggested
that GGPP, but not cholesterol depletion, were responsible for the induction of
neuroprotection. Therefore, we tested whether 3-day treatments with perillic
acid, a nonspecific inhibitor of both geranylgeranyl transferase (GGT) GGT 1 and
Rab GGT, and the GGT 1-specific inhibitor GGTI-286 would reproduce the effects of
RST. Perillic acid, but not GGTI-286, elicited robust neuronal preconditioning
against OGD. RST, GGTI-286, and perillic acid all decreased mitochondrial
membrane potential and lactate dehydrogenase activity in the cultured neurons,
but only RST and perillic acid reduced neuronal ATP and membrane Rab3a protein
levels. In conclusion, RST preconditions cultured neurons against OGD via
depletion of GGPP, leading to decreased geranylgeranylation of proteins that are
probably not isoprenylated by GGT 1. Reduced neuronal ATP levels and ROS
production after OGD may be directly involved in the mechanism of
neuroprotection.
Típus:
Article
PeerReviewed
Formátum:
text
Azonosító:
Domoki, Ferenc and Kis, Béla and Gáspár, Tamás and Bari, Ferenc (2009) Rosuvastatin induces delayed preconditioning against oxygen-glucose deprivation in cultured cortical neurons. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 296 (1). C97-105. ISSN 0363-6143
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