Abstract

The peroxisome is a ubiquitous subcellular organelle and more than 60 proteins responsible for various cellular functions are known to be localized in peroxisomes. The importance of the functions of peroxisomes in cellular biology is underscored by the identification of 17 fatal inherited neurological disorders associated with their dysfunction. In addition to peroxisomal dysfunction in inherited disorders, studies from our laboratory report dysfunction of peroxisomes in inflammatory disease as a result of a decrease in the number of peroxisomes. Based on the importance of peroxisomes in normal cellular biology and related genetic diseases, we hypothesize that inflammatory disease events signal/trigger the process which alters the structure (proteins and lipids) and functions peroxisomes and thus compromises peroxisomal metabolic contribution to cells/tissue indicating a role for peroxisomal biology in the pathology of inflammatory neurological diseases. Secondly, these effects may vary in different cell types of the central nervous system (CNS). Therefore, the proposed studies are designed to investigate the structure/function of peroxisomes in different cell types of CNS and the mechanisms for their alterations under inflammatory conditions.
Specific aims are: 1. To determine the alterations in peroxisomes in different cell types of CNS and the mechanism of their alteration under inflammatory conditions and to investigate the mechanism responsible for these alterations. 2. To investigate the structural/functional alterations in peroxisomes by lipidomic and proteomic analysis of purified peroxisomes from different cell types of CNS. The proposed studies will utilize state of the art techniques in lipidomics and proteomics and will provide a better understanding of the structure and functions of peroxisomes in control tissue and will provide information regarding the role of peroxisomal dysfunction in the pathobiology of the neuroinflammatory disease process. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034741-10
Application #
7071891
Study Section
Special Emphasis Panel (ZRG1-CNBT (01))
Program Officer
Stewart, Randall R
Project Start
1996-04-22
Project End
2009-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
10
Fiscal Year
2006
Total Cost
$322,888
Indirect Cost

  Institution

Name
Medical University of South Carolina
Department
Pediatrics
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425

  Publications

Nie, Xingju; Lowe, Danielle W; Rollins, Laura Grace et al. (2016) Sex-specific effects of N-acetylcysteine in neonatal rats treated with hypothermia after severe hypoxia-ischemia. Neurosci Res 108:24-33
Contreras, Miguel A; Alzate, Oscar; Singh, Avtar K et al. (2014) PPAR? activation induces N(?)-Lys-acetylation of rat liver peroxisomal multifunctional enzyme type 1. Lipids 49:119-31
Paintlia, Manjeet K; Paintlia, Ajaib S; Singh, Avtar K et al. (2011) Synergistic activity of interleukin-17 and tumor necrosis factor-ýý enhances oxidative stress-mediated oligodendrocyte apoptosis. J Neurochem 116:508-21
Khan, Mushfiquddin; Singh, Jaspreet; Gilg, Anne G et al. (2010) Very long-chain fatty acid accumulation causes lipotoxic response via 5-lipoxygenase in cerebral adrenoleukodystrophy. J Lipid Res 51:1685-95
Paintlia, Ajaib S; Paintlia, Manjeet K; Singh, Avtar K et al. (2010) Activation of PPAR-? and PTEN cascade participates in lovastatin-mediated accelerated differentiation of oligodendrocyte progenitor cells. Glia 58:1669-85
Tatar, Carrie L; Appikatla, Sunita; Bessert, Denise A et al. (2010) Increased Plp1 gene expression leads to massive microglial cell activation and inflammation throughout the brain. ASN Neuro 2:e00043
Won, Je-Seong; Im, Yeong-Bin; Kim, Jinsu et al. (2010) Involvement of AMP-activated-protein-kinase (AMPK) in neuronal amyloidogenesis. Biochem Biophys Res Commun 399:487-91
Contreras, Miguel Agustin; Ries, William Louis; Shanmugarajan, Srinivasan et al. (2010) Factors that affect postnatal bone growth retardation in the twitcher murine model of Krabbe disease. Biochim Biophys Acta 1802:601-8
Paintlia, Ajaib S; Paintlia, Manjeet K; Singh, Inderjit et al. (2009) Combination therapy of lovastatin and rolipram provides neuroprotection and promotes neurorepair in inflammatory demyelination model of multiple sclerosis. Glia 57:182-93
Hoda, Md Nasrul; Singh, Inderjit; Singh, Avtar K et al. (2009) Reduction of lipoxidative load by secretory phospholipase A2 inhibition protects against neurovascular injury following experimental stroke in rat. J Neuroinflammation 6:21

Showing the most recent 10 out of 104 publications