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Ochratoxin A and Epigenetics

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Handbook of Nutrition, Diet, and Epigenetics

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Abstract

Ochratoxin A is a thermoresistant mycotoxin produced by ubiquitous molds of Aspergillus and Penicillium genera. It contaminates foodstuffs and feedstuffs worldwide and therefore is of human and animal concern.

Ochratoxin A induces oxidative stress, inflammation, and fibrosis, and is nephrotoxic, hepatotoxic, and neurotoxicin particularly in male subjects. Toxicity is mainly exerted through epigenetic mechanisms.

Nephrotoxicity is probably due to ochratoxin A-induced suppression of the collagen regulator mir-29b that results in an increase of translated collagen, fibrotic alteration, and nephropathy. Alternatively, ochratoxin A induces mir-132 upregulation that occurs in neurologic and psychiatric conditions as well as in oxidative stress. Undeniably, mir-132 acts in the reciprocal regulation of autism-related genes MeCP2 and PTEN decreasing the antioxidant Nrf2 that leads to the formation of high levels of reactive oxygen species. Reactive oxygen species, in turn, enhance the expression of mir-200c that impairs antioxidative mechanisms and synaptic plasticity through the reduction of HO-1 and NLGN4X. As for apoptosis, OTA exposure increases mir-122 that suppresses the anti-apoptotic genes Bcl-w and caspase-3 leading to cell death and hepatic damage.

Interestingly, both MECP2 and NLGN4X are involved in neurodevelopmental disorders, including autism, and are mapped on the X chromosome. As autism is a male predominant disorder, a possible contribution of ochratoxin A in its pathogenesis and in its strong male bias can be suggested.

Very few papers report about ochratoxin A-induced deacetylation:cells exposed to OTA underwent to a dramatic block of histone acetyltransferases leading to mitotic arrest and Nrf2 inhibition that, again, lead to reactive oxygen species formation.

Further studies are needed to obtain a complete picture of ochratoxin A-dependent epigenetic effects and to prevent or to counteract them.

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Abbreviations

AREs:

Antioxidant responsive elements

ASD:

Autism spectrum disorder (ASD)

BACE1:

β-Secretase-1 enzyme

BBB:

Blood brain barrier

BDNF :

Brain-derived neurotropic factor

BEN:

Balkan endemic nephropathy

CASP3 :

Caspase3

CBP:

CREB-binding protein

CNS:

Central nervous system

DGCR8 :

DiGeorge syndrome critical region gene 8

FMRP:

Fragile X mental retardation protein

HAT:

Histone acetyltransferase

HDAC:

Histone deacetylase

HO-1 :

Heme oxygenase-1

MeCP2 :

Methyl-CpG-binding protein 2

NLGN4X :

Neuroligin4x

OTA:

Ochratoxin A

p300:

Adenoviral E1A-associated protein

PAH :

Phenylalanine hydroxylase

phe:

Phenylalanine

PKU:

Phenylketonuria

PTEN :

Phosphatase and tensin homolog

TGFβ:

Transforming-growth factor-beta

Nrf2 :

Nuclear factor erythroid 2-like 2

ROS:

Reactive oxygen species

tyr:

tyrosine

ZEB1 :

Zinc finger E-box binding homeobox 1

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  1. National Research Council, Institute of Biomedical Technologies (CNR-ITB), Via FratelliCervi, 93, 20090, Segrate (MI), Italy

    Alessandra Mezzelani

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  1. c/o Editorial Board 978-0-387-78665 , Heidelberg, Baden-Württemberg, Germany

    Vinood Patel

  2. Kings College , London, United Kingdom

    Victor Preedy

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Mezzelani, A. (2017). Ochratoxin A and Epigenetics. In: Patel, V., Preedy, V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham. https://doi.org/10.1007/978-3-319-31143-2_33-1

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