Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment

Cornelia Franke; Michael Nöldner; Reham Abdel-Kader; Leslie N. Johnson-Anuna; W. Gibson Wood; Walter E. Müller; Gunter P. Eckert

doi:10.1016/j.nbd.2006.10.004

Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment

Cornelia Franke
, Michael Nöldner
, Reham Abdel-Kader
, Leslie N. Johnson-Anuna
, W. Gibson Wood
, Walter E. Müller
, Gunter P. Eckert

Pharmacology

Research output: Contribution to journal › Article › peer-review

85 Scopus citations

Abstract

The present study determined if chronic simvastatin administration in vivo would provide neuroprotection in brain cells isolated from guinea pigs after challenge with the Bcl-2 inhibitor HA 14-1 or the NO donor sodium nitroprusside (SNP). Bcl-2 levels were significantly increased in brains of simvastatin-treated guinea pigs while levels of the pro-apoptotic protein Bax were significantly reduced. The ratio of Bax/Bcl-2, being a critical factor of the apoptotic state of cells, was significantly reduced in simvastatin-treated animals. Cholesterol levels in the brain remained unchanged in the simvastatin group. Brain cells isolated from simvastatin-treated guinea pigs were significantly less vulnerable to mitochondrial dysfunction and caspase-activation. These results provide new insight into potential mechanisms for the protective actions of statins within the CNS where programmed cell death has been implicated.

Original language	English (US)
Pages (from-to)	438-445
Number of pages	8
Journal	Neurobiology of Disease
Volume	25
Issue number	2
DOIs	https://doi.org/10.1016/j.nbd.2006.10.004
State	Published - Feb 2007

Bibliographical note

Funding Information:
This work was supported by the Hannah-Bragard-Apfel-Foundation, Hirnliga and AFI grant No. 02806 and by grants from the National Institutes of Health AG-23524, AG-18357, NATO Collaborative Linkage Grant (980136) and resources/facilities of the Minneapolis VA Medical Center.

Keywords

Bax
Bcl-2
Guinea pigs
HA 14-1
Neuroprotection
SNP
Simvastatin

Publisher link

10.1016/j.nbd.2006.10.004

Find It

Find It at U of M Libraries

Cite this

@article{cfa755111e744463805dd43781340147,

title = "Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment",

abstract = "The present study determined if chronic simvastatin administration in vivo would provide neuroprotection in brain cells isolated from guinea pigs after challenge with the Bcl-2 inhibitor HA 14-1 or the NO donor sodium nitroprusside (SNP). Bcl-2 levels were significantly increased in brains of simvastatin-treated guinea pigs while levels of the pro-apoptotic protein Bax were significantly reduced. The ratio of Bax/Bcl-2, being a critical factor of the apoptotic state of cells, was significantly reduced in simvastatin-treated animals. Cholesterol levels in the brain remained unchanged in the simvastatin group. Brain cells isolated from simvastatin-treated guinea pigs were significantly less vulnerable to mitochondrial dysfunction and caspase-activation. These results provide new insight into potential mechanisms for the protective actions of statins within the CNS where programmed cell death has been implicated.",

keywords = "Bax, Bcl-2, Guinea pigs, HA 14-1, Neuroprotection, SNP, Simvastatin",

author = "Cornelia Franke and Michael N{\"o}ldner and Reham Abdel-Kader and Johnson-Anuna, \{Leslie N.\} and Wood, \{W. Gibson\} and M{\"u}ller, \{Walter E.\} and Eckert, \{Gunter P.\}",

note = "Funding Information: This work was supported by the Hannah-Bragard-Apfel-Foundation, Hirnliga and AFI grant No. 02806 and by grants from the National Institutes of Health AG-23524, AG-18357, NATO Collaborative Linkage Grant (980136) and resources/facilities of the Minneapolis VA Medical Center.",

year = "2007",

month = feb,

doi = "10.1016/j.nbd.2006.10.004",

language = "English (US)",

volume = "25",

pages = "438--445",

journal = "Neurobiology of Disease",

issn = "0969-9961",

publisher = "Academic Press Inc.",

number = "2",

}

TY - JOUR

T1 - Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment

AU - Franke, Cornelia

AU - Nöldner, Michael

AU - Abdel-Kader, Reham

AU - Johnson-Anuna, Leslie N.

AU - Wood, W. Gibson

AU - Müller, Walter E.

AU - Eckert, Gunter P.

N1 - Funding Information: This work was supported by the Hannah-Bragard-Apfel-Foundation, Hirnliga and AFI grant No. 02806 and by grants from the National Institutes of Health AG-23524, AG-18357, NATO Collaborative Linkage Grant (980136) and resources/facilities of the Minneapolis VA Medical Center.

PY - 2007/2

Y1 - 2007/2

N2 - The present study determined if chronic simvastatin administration in vivo would provide neuroprotection in brain cells isolated from guinea pigs after challenge with the Bcl-2 inhibitor HA 14-1 or the NO donor sodium nitroprusside (SNP). Bcl-2 levels were significantly increased in brains of simvastatin-treated guinea pigs while levels of the pro-apoptotic protein Bax were significantly reduced. The ratio of Bax/Bcl-2, being a critical factor of the apoptotic state of cells, was significantly reduced in simvastatin-treated animals. Cholesterol levels in the brain remained unchanged in the simvastatin group. Brain cells isolated from simvastatin-treated guinea pigs were significantly less vulnerable to mitochondrial dysfunction and caspase-activation. These results provide new insight into potential mechanisms for the protective actions of statins within the CNS where programmed cell death has been implicated.

AB - The present study determined if chronic simvastatin administration in vivo would provide neuroprotection in brain cells isolated from guinea pigs after challenge with the Bcl-2 inhibitor HA 14-1 or the NO donor sodium nitroprusside (SNP). Bcl-2 levels were significantly increased in brains of simvastatin-treated guinea pigs while levels of the pro-apoptotic protein Bax were significantly reduced. The ratio of Bax/Bcl-2, being a critical factor of the apoptotic state of cells, was significantly reduced in simvastatin-treated animals. Cholesterol levels in the brain remained unchanged in the simvastatin group. Brain cells isolated from simvastatin-treated guinea pigs were significantly less vulnerable to mitochondrial dysfunction and caspase-activation. These results provide new insight into potential mechanisms for the protective actions of statins within the CNS where programmed cell death has been implicated.

KW - Bax

KW - Bcl-2

KW - Guinea pigs

KW - HA 14-1

KW - Neuroprotection

KW - SNP

KW - Simvastatin

UR - https://www.scopus.com/pages/publications/33846439745

UR - https://www.scopus.com/pages/publications/33846439745#tab=citedBy

U2 - 10.1016/j.nbd.2006.10.004

DO - 10.1016/j.nbd.2006.10.004

M3 - Article

C2 - 17157514

AN - SCOPUS:33846439745

SN - 0969-9961

VL - 25

SP - 438

EP - 445

JO - Neurobiology of Disease

JF - Neurobiology of Disease

IS - 2

ER -

Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment

Abstract

Bibliographical note

Keywords

Publisher link

Find It

Other files and links

Fingerprint

Cite this