Abstract

The overall goal of this project is to understand the role of poly(ADP- ribose)polymerase in the pathogenesis and pathology of neuronal injury following excitotoxicity and ischemia-reperfusion injury. The Viral Gene Transfer Core C, has a central role in the Program Project grant and it will interact closely and support the activities of all three projects. The goals of the Viral Gene Transfer Core C are: 1. To provide adenovirus or sindbus virus vectors for expression of poly(ADP-ribose) polymerase (PARP), PARP mutants, and reporter genes to Projects 1, 2, and 3 for infection of neurons in vitro and in vivo. 2. To make new mutations to the various functional domains of PARP and generate adenovirus or sindbus virus vectors of the new mutations and to make viruses containing poly (ADP-ribose) glycohydrolase (PARG) for use by Projects 1, 2 and 3. The staff of the Viral Gene Transfer Core C have experience in generating and amplifying viral vectors, both adenovirus and sindbus virus. The Viral Gene Transfer Core C will be a shared resource of this Program Project grant and will play a central role in our investigations into the actions of PARP in neuronal injury.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS039148-02
Application #
6349248
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
2000-05-01
Project End
2001-04-30
Budget Start
Budget End
Support Year
2
Fiscal Year
2000
Total Cost
$224,918
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Fatokun, A A; Liu, J O; Dawson, V L et al. (2013) Identification through high-throughput screening of 4'-methoxyflavone and 3',4'-dimethoxyflavone as novel neuroprotective inhibitors of parthanatos. Br J Pharmacol 169:1263-78
Wang, Yingfei; Kim, No Soo; Haince, Jean-Francois et al. (2011) Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos). Sci Signal 4:ra20
Andrabi, Shaida A; Kang, Ho Chul; Haince, Jean-François et al. (2011) Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death. Nat Med 17:692-9
Kang, Ho Chul; Lee, Yun-Il; Shin, Joo-Ho et al. (2011) Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage. Proc Natl Acad Sci U S A 108:14103-8
Li, Xiaoling; Klaus, Judith A; Zhang, Jian et al. (2010) Contributions of poly(ADP-ribose) polymerase-1 and -2 to nuclear translocation of apoptosis-inducing factor and injury from focal cerebral ischemia. J Neurochem 113:1012-22
Xu, Zhenfeng; Zhang, Jian; David, Karen K et al. (2010) Endonuclease G does not play an obligatory role in poly(ADP-ribose) polymerase-dependent cell death after transient focal cerebral ischemia. Am J Physiol Regul Integr Comp Physiol 299:R215-21
Kishimoto, Koji; Li, Rung-Chi; Zhang, Jian et al. (2010) Cytosolic phospholipase A2 alpha amplifies early cyclooxygenase-2 expression, oxidative stress and MAP kinase phosphorylation after cerebral ischemia in mice. J Neuroinflammation 7:42
Wang, Yingfei; Kim, No S; Li, Xiaoling et al. (2009) Calpain activation is not required for AIF translocation in PARP-1-dependent cell death (parthanatos). J Neurochem 110:687-96
Yu, Seong-Woon; Wang, Yingfei; Frydenlund, Didrik S et al. (2009) Outer mitochondrial membrane localization of apoptosis-inducing factor: mechanistic implications for release. ASN Neuro 1:
Wang, Yingfei; Dawson, Valina L; Dawson, Ted M (2009) Poly(ADP-ribose) signals to mitochondrial AIF: a key event in parthanatos. Exp Neurol 218:193-202

Showing the most recent 10 out of 27 publications