Mycotoxin Adducts on Human Serum Albumin: Biomarkers of Exposure to Stachybotrys

[Guest guest]

Note: Performing your original search, Mycotoxin Adducts on Human

Serum Albumin: Biomarkers of Exposure, in PubMed Central will

retrieve 9 citations.Journal List > Environ Health Perspect > v.114

(8); Aug 2006

Related material:

PubMed recordPubMed related artsPubMed

LinkOutCompoundSubstanceTaxonomyTaxonomy tree

PubMed articles by:

Yike, I.

Distler, A.

Ziady, A.

Dearborn, D. Environ Health Perspect. 2006 August; 114(8): 1221–

1226.

Published online 2006 April 26. doi: 10.1289/ehp.9064.

Copyright This is an Open Access article: verbatim copying and

redistribution of this article are permitted in all media for any

purpose, provided this notice is preserved along with the article's

original DOI

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1552036

Research

Mycotoxin Adducts on Human Serum Albumin: Biomarkers of Exposure to

Stachybotrys chartarum

Iwona Yike,1,3 Anne M. Distler,2 Assem G. Ziady,1 and Dorr G.

Dearborn1,3

1 Departments of Pediatrics and

2 Pharmacology and

3 Ann Swetland Center for Environmental Health, Case Western

Reserve University, Cleveland, Ohio, USA

Address correspondence to D.G. Dearborn, Swetland Center for

Environmental Health, Case Western Reserve University, School of

Medicine, 10900 Euclid Ave., Cleveland, OH 44106-4948 USA.

Telephone: (216) 368-8521. Fax: (216) 368-4518. E-mail: dxd9@...

The authors declare they have no competing financial interests.

Received February 2, 2006; Accepted April 26, 2006.

Top

Abstract

Materials and Methods

Results

Discussion

References Abstract Objective.

Despite the growing body of evidence showing adverse health effects

from inhalation exposure to the trichothecene-producing mold

Stachybotrys chartarum, controversy remains. Currently, there are no

reliable assays suitable for clinical diagnosis of exposure. We

hypothesized that satratoxin G (SG)–albumin adducts may serve as

biomarkers of exposure to this fungus.

Design. We studied the formation of adducts of SG with serum albumin

in vitro using Western blots and mass spectrometry (MS) and searched

for similar adducts formed in vivo using human and animal serum.

Results. Samples of purified human serum albumin that had been

incubated with increasing concentrations of SG showed concentration-

dependent albumin bands in Western blots developed with anti-SG

antibodies. MS analysis found that as many as 10 toxin molecules can

be bound in vitro to one albumin molecule. The sequencing of albumin-

adduct tryptic peptides and the analysis of pronase/aminopeptidase

digests demonstrated that lysyl, cysteinyl, and histidyl residues

are involved in the formation of these adducts. Serum samples from

three patients with documented exposure to S. chartarum similarly

revealed lysine–, cysteine–, and histidine–SG adducts after

exhaustive digestion, affinity column enrichment, and MS analysis.

These adducts were also found in the sera from rats exposed to the

spores of S. chartarum in contrast to control human subjects and

control animals.

Conclusions. These data document the occurrence of SG–albumin

adducts in both in vitro experiments and in vivo human and animal

exposures to S. chartarum.

Relevance to clinical practice. SG–amino acid adducts may serve as

reliable dosimeter biomarkers for detection of exposure to S.

chartarum.

Keywords: biomarkers, satratoxin G, Stachybotrys chartarum,

trichothecenes

[Guest guest]

so basicly, mycotoxin adduvts cause vasculitis and oxidaruve

stress/onoo and punches holes in blood vessel walls and causes plaque

build up. evem in the brain.

--- In , " tigerpaw2c " <tigerpaw2c@...>

wrote:

>

> Note: Performing your original search, Mycotoxin Adducts on

Human

> Serum Albumin: Biomarkers of Exposure, in PubMed Central will

> retrieve 9 citations.Journal List > Environ Health Perspect > v.114

> (8); Aug 2006

>

> Related material:

> PubMed recordPubMed related artsPubMed

> LinkOutCompoundSubstanceTaxonomyTaxonomy tree

>

> PubMed articles by:

> Yike, I.

> Distler, A.

> Ziady, A.

> Dearborn, D. Environ Health Perspect. 2006 August; 114(8): 1221–

> 1226.

>

> Published online 2006 April 26. doi: 10.1289/ehp.9064.

> Copyright This is an Open Access article: verbatim copying and

> redistribution of this article are permitted in all media for any

> purpose, provided this notice is preserved along with the article's

> original DOI

>

> http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1552036

>

>

> Research

> Mycotoxin Adducts on Human Serum Albumin: Biomarkers of Exposure to

> Stachybotrys chartarum

> Iwona Yike,1,3 Anne M. Distler,2 Assem G. Ziady,1 and Dorr G.

> Dearborn1,3

> 1 Departments of Pediatrics and

> 2 Pharmacology and

> 3 Ann Swetland Center for Environmental Health, Case Western

> Reserve University, Cleveland, Ohio, USA

>

> Address correspondence to D.G. Dearborn, Swetland Center for

> Environmental Health, Case Western Reserve University, School of

> Medicine, 10900 Euclid Ave., Cleveland, OH 44106-4948 USA.

> Telephone: (216) 368-8521. Fax: (216) 368-4518. E-mail: dxd9@...

>

> The authors declare they have no competing financial interests.

>

> Received February 2, 2006; Accepted April 26, 2006.

> Top

> Abstract

> Materials and Methods

> Results

> Discussion

> References Abstract Objective.

>

> Despite the growing body of evidence showing adverse health effects

> from inhalation exposure to the trichothecene-producing mold

> Stachybotrys chartarum, controversy remains. Currently, there are

no

> reliable assays suitable for clinical diagnosis of exposure. We

> hypothesized that satratoxin G (SG)–albumin adducts may serve as

> biomarkers of exposure to this fungus.

>

> Design. We studied the formation of adducts of SG with serum

albumin

> in vitro using Western blots and mass spectrometry (MS) and

searched

> for similar adducts formed in vivo using human and animal serum.

>

> Results. Samples of purified human serum albumin that had been

> incubated with increasing concentrations of SG showed concentration-

> dependent albumin bands in Western blots developed with anti-SG

> antibodies. MS analysis found that as many as 10 toxin molecules

can

> be bound in vitro to one albumin molecule. The sequencing of

albumin-

> adduct tryptic peptides and the analysis of pronase/aminopeptidase

> digests demonstrated that lysyl, cysteinyl, and histidyl residues

> are involved in the formation of these adducts. Serum samples from

> three patients with documented exposure to S. chartarum similarly

> revealed lysine–, cysteine–, and histidine–SG adducts after

> exhaustive digestion, affinity column enrichment, and MS analysis.

> These adducts were also found in the sera from rats exposed to the

> spores of S. chartarum in contrast to control human subjects and

> control animals.

>

> Conclusions. These data document the occurrence of SG–albumin

> adducts in both in vitro experiments and in vivo human and animal

> exposures to S. chartarum.

>

> Relevance to clinical practice. SG–amino acid adducts may serve as

> reliable dosimeter biomarkers for detection of exposure to S.

> chartarum.

>

> Keywords: biomarkers, satratoxin G, Stachybotrys chartarum,

> trichothecenes

>

[Guest guest]

Here is an interesting paper on the use of NAC to reduce oxidative stress to

the lungs to prevent coughing up blood from this rare disease.

http://www.eurekalert.org/pub_releases/2007-06/uol-wfm053107.php

Contact: Dr. Marcus Cooke

44-011-625-2825

University of Leicester <http://www.leicester.ac.uk/>

World first medical treatment announced by researchers Breakthrough in

research and treatment of rare but devastating condition

Researchers at Queen University London and the University of Leicester

and have today (Friday June 1) announced a potential breakthrough in the

treatment of a rare but devastating medical condition that can affect

children and young people.

In a world first, the clinicians and scientists from the two universities

have already treated one patient with promising results. Their preliminary

data are published as a letter in the New England Journal of Medicine.

This is the first time research into a condition known as " idiopathic

pulmonary haemosiderosis " has investigated the role of 'oxidative stress'

and it is also the first time treatment has been carried out based on the

research.

Queen University London and the University of Leicester have combined

world-class expertise in Child Health, Pulmonary Disease and Oxidative

Stress research, plus access to patients with this rare disease. This

combination of factors is unique to this collaboration.

Grigg, Professor of Paediatric Respiratory and Environmental

Medicine at Queen University London, said: " Idiopathic pulmonary

haemosiderosis is a rare disease, the cause of which is unknown.

" Affected patients have episodes of bleeding in the lungs, which often need

hospital admissions, and in some cases it can be life threatening. This is

normally combated by the use of continuous oral steroids (which can have

major side effects).

" In a child local to Leicester, we were able to show, for the first time,

that there was high levels of oxidative stress in the lungs. In addition, we

treated the increased oxidative stress by using of an antioxidant, N-acetyl

cysteine - which has no side effects. Since she has been on this treatment

she has had no lung bleeds, and the steroid dose has been significantly

reduced. "

Dr Marcus Cooke, Senior lecturer in the Radiation and Oxidative Stress

Section at the University of Leicester, added: " It is a really good feeling

to be involved in a project looking at oxidative stress, that can make such

an enormous difference to a person's quality of life.

" I think that we will see an increasing use of biomarkers of oxidative

stress to support clinical decisions. "

Dr Cooke said that idiopathic pulmonary haemosiderosis is a devastating

condition. Characteristic of this condition is the accumulation of

protein-bound iron in the lungs, a consequence of repeated bleeding in the

lungs, coupled with inflammation and fibrosis. Ultimately this condition is

usually fatal. Treatment to prevent the lung damage and prevent anaemia is a

combination of corticosteroids and iron supplement.

Both chronic inflammation, and the presence of iron, released following

bleeding into the lungs, can lead to a condition known as oxidative stress.

Oxidative stress occurs when the production of free radicals, highly

reactive chemicals, outweighs antioxidant defences. This leads to a great

deal of damage to cells, and in particular DNA, the cell's 'blueprint', and

is likely to be responsible for the fibrosis, as the lungs try to repair the

damage done by free radicals.

" In order to establish whether oxidative stress was indeed associated with

episodes of bleeding into the lungs, we measured a biomarker of oxidative

stress, and a marker of damage to DNA specifically, in urine.

" We noted that levels of oxidative stress increased significantly following

every bleed. With this in mind, and on the basis that antioxidants can

potentially boost the body's natural defences, we began the patient on a

course of the antioxidant drug N-acetyl cysteine. Five months into

antioxidant therapy, the patient remains clinically well, and on a reduced

dose of corticosteroids. "