|Author||Ben Salem, Intidhar ♦ Boussabbeh, Manel|
|Source||United States Department of Energy Office of Scientific and Technical Information|
|Subject Keyword||APPLIED LIFE SCIENCES ♦ APOPTOSIS ♦ CEREALS ♦ FUSARIUM ♦ INHIBITION ♦ METABOLITES ♦ MITOCHONDRIA ♦ MYCOTOXINS ♦ TOXICITY|
|Abstract||Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. The major ZEN metabolites are α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL). In the present study, we investigated the underlying mechanism of the toxicity induced by ZEN, α-ZOL and β-ZOL in cardiac cells (H9c2). We show that treatment with ZEN or its metabolites induces the activation of the mitochondrial pathway of apoptosis as characterized by an increase in ROS generation, a loss of mitochondrial transmembrane potential (ΔΨm) and an activation of caspases. Besides, we demonstrate that these mycotoxins promote the activation of autophagy before the onset of apoptosis. Indeed, we observed that a short-time (6 h) treatment with ZEN, α-ZOL or β-ZOL, increased the level of Beclin-1 and LC3-II and induced the accumulation of the CytoID® autophagy detection probe. Moreover, the inhibition of autophagy by Chloroquine significantly increased cell death induced by ZEN, α-ZOL or β-ZOL, suggesting that the activation of autophagy serves as a cardioprotective mechanism against these mycotoxins. In addition, we found that the inhibition (EX527) or the knockdown of SIRT1 (siRNA) significantly increased apoptosis induced by ZEN or its derivatives, whereas SIRT1 activation with RSV greatly prevents the cytotoxic effects of these mycotoxins. By contrast, when autophagy was inhibited by CQ, the activation of SIRT1 by RSV had no protection against the cardiotoxicity of ZEN or its metabolites, suggesting that SIRT1 protects cardiac cells by an autophagy-dependent pathway. - Highlights: • ZEN, α- and β-ZOL induce the mitochondrial pathway of apoptosis in cardiac cells. • Inhibition of autophagy enhanced ZEN-, α-ZOL- and β-ZOL-induced apoptosis. • SIRT1 activates autophagy to protect cells from ZEN, α- and β-ZOL-induced toxicity.|
|Learning Resource Type||Article|
|Publisher Place||United States|
|Journal||Toxicology and Applied Pharmacology|
Ministry of Human Resource Development (MHRD) under its National Mission on Education through Information and Communication Technology (NMEICT) has initiated the National Digital Library of India (NDLI) project to develop a framework of virtual repository of learning resources with a single-window search facility. Filtered and federated searching is employed to facilitate focused searching so that learners can find out the right resource with least effort and in minimum time. NDLI is designed to hold content of any language and provides interface support for leading vernacular languages, (currently Hindi, Bengali and several other languages are available). It is designed to provide support for all academic levels including researchers and life-long learners, all disciplines, all popular forms of access devices and differently-abled learners. It is being developed to help students to prepare for entrance and competitive examinations, to enable people to learn and prepare from best practices from all over the world and to facilitate researchers to perform inter-linked exploration from multiple sources. It is being developed at Indian Institute of Technology Kharagpur.
NDLI is a conglomeration of freely available or institutionally contributed or donated or publisher managed contents. Almost all these contents are hosted and accessed from respective sources. The responsibility for authenticity, relevance, completeness, accuracy, reliability and suitability of these contents rests with the respective organization and NDLI has no responsibility or liability for these. Every effort is made to keep the NDLI portal up and running smoothly unless there are some unavoidable technical issues.
Ministry of Human Resource Development (MHRD), through its National Mission on Education through Information and Communication Technology (NMEICT), has sponsored and funded the National Digital Library of India (NDLI) project.
For any issue or feedback, please write to firstname.lastname@example.org