NIDS-related/phosphatidylserine-Autism,Alzheimer disease, Parkinson disease,

[Guest guest]

1-Alteration in amino-glycerophospholipids levels in the plasma of children

with autism: a potential biochemical diagnostic marker.

2-Essential cellular regulatory elements of oxidative stress in early and

late phases of apoptosis in the central nervous system.

3-Apoptotic cells as sources for biologically active oxidized phospholipids.

4-Rat brain arachidonic acid metabolism is increased by a 6-day

intracerebral ventricular infusion of bacterial lipopolysaccharide.

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Life Sci. 2004 Feb 13;74(13):1635-43.

Alteration in amino-glycerophospholipids levels in the plasma of children

with autism: a potential biochemical diagnostic marker.

Chauhan V, Chauhan A, Cohen IL, Brown WT, Sheikh A.

NYS Institute for Basic Research in Developmental Disabilities, Staten

Island, New York, NY 10314, USA. chauhanvps@...

Currently, there is no biochemical test to assist in the behavioral

diagnosis of autism.

We observed that levels of phosphatidylethanolamine (PE) were decreased

while phosphatidylserine (PS) were increased in the erythrocyte membranes of

children with autism as compared to their non-autistic developmentally

normal siblings.

A new method using Trinitrobenezene sulfonic acid (TNBS) for the

quantification of PE and PS (amino-glycerophospholipids, i.e., AGP) in the

plasma of children was developed and standardized. Wavelength scans of

TNBS-PE and TNBS-PS complexes gave two peaks at 320 nm and 410 nm. When

varying concentrations of PS and PE were used, a linear regression line was

observed at 410 nm with TNBS.

Using this assay, the levels of AGP were found to be significantly increased

in the plasma of children with autism as compared to their non-autistic

normal siblings. It is proposed that plasma AGP levels may function as a

potential diagnostic marker for autism.

PMID: 14738907 [PubMed - indexed for MEDLINE]

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Antioxid Redox Signal. 2004 Apr;6(2):277-87.

Essential cellular regulatory elements of oxidative stress in early and late

phases of apoptosis in the central nervous system.

Chong ZZ, Kang JQ, Maiese K.

Division of Cellular and Molecular Cerebral Ischemia, Center for Molecular

Medicine and Genetics, and Institute of Environmental Health Sciences, Wayne

State University School of Medicine, Detroit, MI 48201.

The generation of reactive oxygen species and subsequent oxidative stress in

the central nervous system is now considered to be one of the primary

etiologies of a host of neurodegenerative disorders, such as Alzheimer

disease, Parkinson disease, and cerebral ischemia.

On a cellular level, oxidative stress leads to an apoptotic early phase that

involves cellular membrane phosphatidylserine (PS) exposure and a late phase

that pertains to the degradation of genomic DNA.

The translocation of membrane PS from the inner cellular membrane to the

surface is a critical component for both microglial activation and cellular

disposal of injured cells. During oxidative stress, this early phase of

apoptosis is intimately controlled by neuronal PS exposure and microglial PS

receptor expression.

The late phase of apoptosis that involves a loss of genomic DNA integrity

can result as a function of an ill-fated attempt to enter the cell cycle in

postmitotic neurons.

By using a cascade of pathways that involve cysteine proteases to modulate

programmed cell death, protein kinase B (Akt) surfaces as a key regulatory

element of both extrinsic pathways of inflammation and intrinsic pathways of

cellular integrity.

Further understanding of the cellular mechanisms modulating neuronal

cellular integrity and phagocytic cell disposal during oxidative stress may

form the basis for the future development of cytoprotective strategies in

the nervous system.

PMID: 15025929 [PubMed - in process]

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Antioxid Redox Signal. 2004 Apr;6(2):311-20.

Apoptotic cells as sources for biologically active oxidized phospholipids.

Kadl A, Bochkov VN, Huber J, Leitinger N.

Department of Vascular Biology and Thrombosis Research, Medical University

of Vienna, Vienna, Austria.

Acute inflammation is characterized by an accumulation of polymorphonuclear

cells (PMNs), generation of reactive oxygen species, subsequent apoptosis of

PMNs, and finally phagocytosis of apoptotic cells by macrophages. Recently,

it has been demonstrated that during apoptosis oxidation of membrane

phospholipids, especially phosphatidylserine, occurs.

Moreover, we have shown that membrane vesicles released from apoptotic cells

contain biologically active oxidized phospholipids. The involvement of

oxidized phospholipids in the development of atherosclerosis, which is

described as a chronic inflammatory disease, is increasingly recognized.

These oxidized phospholipids were shown to induce several proinflammatory

genes, such as monocyte chemoattractant protein 1 or interleukin-8, and it

is hypothesized that lipid oxidation products also play a role in other

chronic inflammatory disorders.

On the other hand, oxidized phospholipids were shown to exert antiendotoxin

effects by inhibiting lipopolysaccharide-induced signaling, representing a

possible feedback loop during gram-negative infection. Additionally, it has

been described that oxidized phospholipids are capable of inducing genes

such as heme oxygenase-1 that are important for the resolution of acute

inflammation.

Moreover, oxidized phospholipids serve as recognition signals on apoptotic

cells facilitating phagocytosis. In this review, we discuss the hypothesis

that oxidized phospholipids generated in apoptotic cells (a) propagate

chronic inflammation and ( contribute to the resolution of acute

inflammation.

PMID: 15025932 [PubMed - in process]

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J Neurochem. 2004 Mar;88(5):1168-78.

Rat brain arachidonic acid metabolism is increased by a 6-day intracerebral

ventricular infusion of bacterial lipopolysaccharide.

Rosenberger TA, Villacreses NE, Hovda JT, Bosetti F, Weerasinghe G, Wine RN,

Harry GJ, Rapoport SI.

Brain Physiology and Metabolism Section, National Institute on Aging,

National Institutes of Health, Bethesda, land 20892-1582, USA.

plsetn@...

In a rat model of acute neuroinflammation, produced by a 6-day intracerebral

ventricular infusion of bacterial lipopolysaccharide (LPS), we measured

brain activities and protein levels of three phospholipases A2 (PLA2) and of

cyclo-oxygenase-1 and -2, and quantified other aspects of brain phospholipid

and fatty acid metabolism.

The 6-day intracerebral ventricular infusion increased lectin-reactive

microglia in the cerebral ventricles, pia mater, and the glial membrane of

the cortex and resulted in morphological changes of glial fibrillary acidic

protein (GFAP)-positive astrocytes in the cortical mantel and areas

surrounding the cerebral ventricles. LPS infusion increased brain cytosolic

and secretory PLA2 activities by 71% and 47%, respectively, as well as the

brain concentrations of non-esterified linoleic and arachidonic acids, and

of prostaglandins E2 and D2.

LPS infusion also increased rates of incorporation and turnover of

arachidonic acid in phosphatidylethanolamine, plasmenylethanolamine,

phosphatidylcholine, and plasmenylcholine by 1.5- to 2.8-fold, without

changing these rates in phosphatidylserine or phosphatidylinositol.

These observations suggest that selective alterations in brain arachidonic

acid metabolism involving cytosolic and secretory PLA2 contribute to early

pathology in neuroinflammation.

PMID: 15009672 [PubMed - in process]

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