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J Nephropathol. 2013;2(3): 166-180.
doi: 10.12860/JNP.2013.28
PMID: 24475446
PMCID: PMC3891133
Scopus ID: 84900308088
  Abstract View: 3234
  PDF Download: 1598

Original Article

Prostaglandin D2 synthase: Apoptotic factor in alzheimer plasma, inducer of reactive oxygen species, inflammatory cytokines and dialysis dementia

John K. Maesaka 1*, Bali Sodam 1, Thomas Palaia 1, Louis Ragolia 1, Vecihi Batuman 2, Nobuyuki Miyawaki 1, Shubha Shastry 1, Steven Youmans 3, Marwan El-Sabban 4
*Corresponding Author: *Corresponding author:DR. John K. Maesaka, 200 Old Country Road Suite 135 Mineola, N.Y. 11501. USA. Tel: 516-663-2169, FAX: 516-663-2179,, Email: jmaesaka@winthrop.org

Abstract

Background: Apoptosis, reactive oxygen species (ROS) and inflammatory cytokines have all been implicated in the development of Alzheimer’s disease (AD).

Objectives: The present study identifies the apoptotic factor that was responsible for the fourfold increase in apoptotic rates that we previously noted when pig proximal tubule, LLC-PK1, cells were exposed to AD plasma as compared to plasma from normal controls and multi-infarct dementia.

Patients and Methods: The apoptotic factor was isolated from AD urine and identified as lipocalin-type prostaglandin D2 synthase (L-PGDS). L-PGDS was found to be the major apoptotic factor in AD plasma as determined by inhibition of apoptosis approximating control levels by the cyclo-oxygenase (COX) 2 inhibitor, NS398, and the antibody to L-PGDS. Blood levels of L-PGDS, however, were not elevated in AD. We now demonstrate a receptor-mediated uptake of L-PGDS in PC12 neuronal cells that was time, dose and temperature-dependent and was saturable by competition with cold L-PGDS and albumin. Further proof of this endocytosis was provided by an electron microscopic study of gold labeled L-PGDS and immunofluorescence with Alexa-labeled L-PGDS.

Results: The recombinant L-PGDS and wild type (WT) L-PGDS increased ROS but only the WTL-PGDS increased IL6 and TNFα, suggesting that differences in glycosylation of L-PGDS in AD was responsible for this discrepancy.

Conclusions: These data collectively suggest that L-PGDS might play an important role in the development of dementia in patients on dialysis and of AD.


Implication for health policy/practice/research/medical education:

Lipocalin-type prostaglandin D2 synthase might play an important role in the development of dementia in patients on dialysis and of Alzheimer’s disease.  

Please cite this paper as:Maesaka JK, Sodam B, Palaia T, Ragolia L, Batuman V, Miyawaki N, Shastry S, Youmans S, El-Saban M. Prostaglandin D2 synthase: Apoptotic factor in alzheimer plasma, inducer of reactive oxygen species, inflammatory cytokines and dialysis dementia. J Nephropathology. 2013; 2(3): 166-180. DOI: 10.12860/JNP.2013.28

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ePublished: 01 Jul 2013
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