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The zinc matrix metalloproteinase ZMP-2 increases survival of Caenorhabditis elegans through interference with lipoprotein absorption.
- Source :
-
Genes & nutrition [Genes Nutr] 2014 Jul; Vol. 9 (4), pp. 414. Date of Electronic Publication: 2014 Jun 24. - Publication Year :
- 2014
-
Abstract
- Matrix metalloproteinases are zinc-dependent endopeptidases conserved throughout the animal kingdom which primarily degrade components of the extracellular matrix. In the nematode Caenorhabditis elegans, the zinc matrix metalloproteinase (ZMP-2) was demonstrated to increase resistance versus heat and bacterial pathogens. Here, we show that the survival reducing activities caused by the knockdown of zmp-2 in C. elegans essentially requires the presence of vitellogenin-6, a protein homologous to mammalian apolipoprotein B, and RME-2, a receptor mediating endocytosis of cholesterol particles. Measurements of reactive oxygen species inside and outside C. elegans revealed that knockdown of zmp-2 causes a prooxidative extracellular mileu which is a prerequisite for the reduction of survival. Interestingly, RNAi for the foxo transcription factor daf-16 completely prevented those survival reducing effects of zmp-2 RNAi, and RNAi in mutants of the steroid signalling pathway revealed that DAF-16 acts by inhibition of DAF-9 and DAF-12. In conclusion, our study demonstrates survival reducing activities caused by the functional loss of ZMP-2 in C. elegans. Those effects are mediated by the transport of oxidized cholesterol adducts which then trigger the inhibition of DAF-9 and DAF-12 through the activation of DAF-16.
Details
- Language :
- English
- ISSN :
- 1555-8932
- Volume :
- 9
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Genes & nutrition
- Publication Type :
- Academic Journal
- Accession number :
- 24957743
- Full Text :
- https://doi.org/10.1007/s12263-014-0414-6