Effect of Aspergillus terreus mycotoxins on nitric oxide synthase activity in hu

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Research Article

Effect of Aspergillus terreus mycotoxins on nitric oxide synthase

activity in human erythroid K-562 cells

A. Pugliese 1 *, A. Savarino 1, V. Vidotto 1, C. Cantamessa 1, G. P.

Pescarmona 2

1Department of Medical and Surgical Science, University of Torino,

Torino, Italy

2Department of Genetics, Biology and Medical Chemistry, University

of Torino, Torino, Italy

http://www3.interscience.wiley.com/journal/40006232/abstract?

CRETRY=1 & SRETRY=0

email: A. Pugliese (gipi@...)

*Correspondence to A. Pugliese, Department of Medical and Surgical

Sciences, University of Turin, Hospital Amedeo di Savoia-C.so

Svizzera 164, I-10149 Turin, Italy.

Funded by:

Italian Ministry for University and Scientific Research (MURST)

Keywords

Aspergillus terreus mycotoxins; cell death; Escherichia coli

lipopolysaccharide; human erythroleukaemic cells; iron; nitric oxide

synthase

Abstract

Because several stimuli of microbial origin enhance the activity of

nitric oxide synthase (NOS) in human cells of the myeloid lineage,

we decided to investigate whether cellular damage induced by

Aspergillus terreus mycotoxins could be associated with an increase

in NOS activity. A pool of mycotoxins rather than individual toxins

was tested so that the natural conditions could be mimicked. In the

present study, we report that a crude extract of A. terreus induces

cellular damage and increases NOS activity in K-562 cells, an

erythroleukaemic cell line in which NOS is particularly active. The

specificity of this association was further investigated by using

NOS inhibitors and by comparing, in the same cellular model, the

effects of the extract with the activity of other microbial toxins

of a defined mechanism of action. Canavanine, an inhibitor of NOS,

significantly reduced cell death in the presence of the extract,

suggesting that cellular damage, induced by the mycotoxins of A.

terreus is at least in part mediated by NOS activity. Moreover,

Escherichia coli lipopolysaccharide (LPS), known to be a potent NOS

inducer, increased NOS activity in our experimental model as well.

In contrast, Bordetella pertussis toxin did not show any effect on

NOS activity. The results of this study suggest that NOS may be

involved in mycotoxicoses. Copyright © 1999 Wiley & Sons, Ltd.

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Received: 7 August 1998; Accepted: 23 September 1998

Cell Biochemistry and Function

Volume 17 Issue 1, Pages 35 - 45

Published Online: 22 Feb 1999