Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response.

Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response. Research Abstract Details 

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Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response. Abstract Text:

Junghee Lee,Bela Kosaras,Hossein Aleyasin,Jeong A Han,David S Park,Rajiv R Ratan,Neil W Kowall,Robert J Ferrante,Sam W Lee,Hoon Ryu,

Cyclooxygenase-2 (COX-2) has been implicated in neuronal survival and death. However, the precise regulatory mechanisms involved in COX-2 function are unclear. In the present study we found that COX-2 is induced in response to glutathione depletion-induced oxidative stress in primary cortical neurons. Two proximal specific Sp1 and Sp3 binding sites are responsible for the COX-2 promoter activity under normal as well as oxidative stress conditions through enhanced Sp1 and Sp3 DNA binding activity. Site-directed mutagenesis confirmed that -268/-267 positions serve as specific Sp1 and Sp3 recognition sites under oxidative stress. Enforced expression of Sp1 and Sp3 using HSV vectors increased the promoter activity, transcription, and protein level of COX-2 in cortical neurons. The dominant negative form of Sp1 abrogated the oxidative stress-induced promoter activity and expression of COX-2. We also demonstrated that adenovirus-mediated COX-2 gene delivery protected neurons from DNA damage induced by oxidative, genotoxic, and excitotoxic stresses and by ischemic injury. Moreover, COX-2(-/-) cortical neurons were more susceptible to DNA damage-induced cell death. These results indicate that in primary neurons Sp1 and Sp3 play an essential role in the modulation of COX-2 transcription, which mediates neuronal homeostasis and survival by preventing DNA damage in response to neuronal stress.

Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response. Publishing Authors By Initials

J Lee,B Kosaras,H Aleyasin,JA Han,DS Park,RR Ratan,NW Kowall,RJ Ferrante,SW Lee,H Ryu,

For similar proteins: dna-binding proteins: kruppel-like transcription factors: sp transcription factors: sp2 transcription factor research abstracts see: proteins: dna-binding proteins: kruppel-like transcription factors: sp transcription factors: sp2 transcription factor research

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Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The FASEB journal : official publication of the Fe

VOLUME: 20

Page Numbers: 2375-7

Journal Abbreviation: FASEB J.

ISSN: 1530-6860

DAY: 28

MONTH: 09

YEAR: 2006

Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8804484

Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response. Keywords Mesh Terms:

KEYWORDS: Sp2 Transcription Factor

MESH TERMS: metabolism

Chemical & Substance for Abstract: Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response. Information

Substance Name: Cyclooxygenase 2

Registry Number: EC 1.14.99.1

Grant and Affiliation Information for Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response.

AFFILIATION: Geriatric Research Education and Clinical Center, Bedford Veteran's Affairs Medical Center, 200 Springs Rd., Bedford, MA 01730, USA.

Country: United States

AGENCY: United States NIA

GRANT: P30 AG13846

ACRONYM: AG

MEDLINETA: FASEB J

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