Cationic amphiphilic drugs are potent inhibitors of yeast sporulation.

Meiosis is a highly regulated developmental process that occurs in all eukaryotes that engage in sexual reproduction. Previous epidemiological work shows that male and female infertility is rising and environmental factors, including pollutants such as organic solvents, are thought to play a role in...

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Autores principales:	Ulrich Schlecht, Robert P St Onge, Thomas Walther, Jean-Marie François, Ronald W Davis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e4df29abced54fc8a7c49432beafd2f5
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spelling	oai:doaj.org-article:e4df29abced54fc8a7c49432beafd2f52021-11-18T07:09:17ZCationic amphiphilic drugs are potent inhibitors of yeast sporulation.1932-620310.1371/journal.pone.0042853https://doaj.org/article/e4df29abced54fc8a7c49432beafd2f52012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22905177/?tool=EBIhttps://doaj.org/toc/1932-6203Meiosis is a highly regulated developmental process that occurs in all eukaryotes that engage in sexual reproduction. Previous epidemiological work shows that male and female infertility is rising and environmental factors, including pollutants such as organic solvents, are thought to play a role in this phenomenon. To better understand how organic compounds interfere with meiotic development, the model organism Saccharomyces cerevisiae was exposed to 446 bioactive molecules while undergoing meiotic development, and sporulation efficiency was quantified employing two different high-throughput assays. 12 chemicals were identified that strongly inhibited spore formation but did not interfere with vegetative growth. Many of these chemicals are known to bind to monoamine-receptors in higher eukaryotes and are cationic amphiphilic drugs. A detailed analysis of one of these drugs, tripelennamine, revealed that it induces sporulation-specific cytotoxicity and a strong inhibition of meiotic M phase. The drug, however, only mildly interfered with pre-meiotic DNA synthesis and the early meiotic transcriptional program. Chemical-genomic screening identified genes involved in autophagy as hypersensitive to tripelennamine. In addition, we found that growing and sporulating yeast cells heterozygous for the aminophospholipid translocase, NEO1, are haploinsufficient in the presence of the drug.Ulrich SchlechtRobert P St OngeThomas WaltherJean-Marie FrançoisRonald W DavisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42853 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ulrich Schlecht Robert P St Onge Thomas Walther Jean-Marie François Ronald W Davis Cationic amphiphilic drugs are potent inhibitors of yeast sporulation.
description	Meiosis is a highly regulated developmental process that occurs in all eukaryotes that engage in sexual reproduction. Previous epidemiological work shows that male and female infertility is rising and environmental factors, including pollutants such as organic solvents, are thought to play a role in this phenomenon. To better understand how organic compounds interfere with meiotic development, the model organism Saccharomyces cerevisiae was exposed to 446 bioactive molecules while undergoing meiotic development, and sporulation efficiency was quantified employing two different high-throughput assays. 12 chemicals were identified that strongly inhibited spore formation but did not interfere with vegetative growth. Many of these chemicals are known to bind to monoamine-receptors in higher eukaryotes and are cationic amphiphilic drugs. A detailed analysis of one of these drugs, tripelennamine, revealed that it induces sporulation-specific cytotoxicity and a strong inhibition of meiotic M phase. The drug, however, only mildly interfered with pre-meiotic DNA synthesis and the early meiotic transcriptional program. Chemical-genomic screening identified genes involved in autophagy as hypersensitive to tripelennamine. In addition, we found that growing and sporulating yeast cells heterozygous for the aminophospholipid translocase, NEO1, are haploinsufficient in the presence of the drug.
format	article
author	Ulrich Schlecht Robert P St Onge Thomas Walther Jean-Marie François Ronald W Davis
author_facet	Ulrich Schlecht Robert P St Onge Thomas Walther Jean-Marie François Ronald W Davis
author_sort	Ulrich Schlecht
title	Cationic amphiphilic drugs are potent inhibitors of yeast sporulation.
title_short	Cationic amphiphilic drugs are potent inhibitors of yeast sporulation.
title_full	Cationic amphiphilic drugs are potent inhibitors of yeast sporulation.
title_fullStr	Cationic amphiphilic drugs are potent inhibitors of yeast sporulation.
title_full_unstemmed	Cationic amphiphilic drugs are potent inhibitors of yeast sporulation.
title_sort	cationic amphiphilic drugs are potent inhibitors of yeast sporulation.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/e4df29abced54fc8a7c49432beafd2f5
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_version_	1718423887228698624

Cationic amphiphilic drugs are potent inhibitors of yeast sporulation.

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