Release of exosomes and microvesicles harbouring specific RNAs and glycosylphosphatidylinositol-anchored proteins from rat and human adipocytes is controlled by histone methylation

Günter Müller, Marion Schneider, Johann Gassenhuber, Susanne Wied
2012 American Journal of Molecular Biology  
The transfer of proteins and nucleic acids from donor to acceptor cells via small membrane vesicles has been implicated with (patho)physiological consequences. Previously the upregulation of esterification and downregulation of lipolysis in small rat adipocytes upon incubation with exosomes and microvesicles (EMVs) released from large adipocytes and harbouring the glycosylphosphatidylinositol (GPI)-anchored proteins, Gce1 and CD73, transcripts specific for FSP27 and GPAT3, and microRNAs, miR-16
more » ... d microRNAs, miR-16 and miR-222 were demonstrated. Here the release of EMVs from large (but not small) primary rat and differentiated rat and human adipocytes in response to palmitate, H 2 O 2 and the anti-diabetic sulfonylurea, glimepiride, is shown to be significantly reduced upon inhibition of histone H3 lysine9 methyltransferase G9a by trans-2-phenylcyclopropylamine (tPCPA) and histone H3 lysine4 demethylase LSD1 by BIX01294. Inhibition of EMV release by tPCPA and BIX01294 was not caused by apoptosis but accompanied by upregulation of the H 2 O 2 -induced stimulation of lipid synthesis and downregulation of lipolysis in large (but not small) primary and differentiated rat and human adipocytes. In contrast, the simultaneous presence of tPCPA and BIX-01294 had almost no effect on the induced release of EMVs and lipid metabolism. These findings argue for regulation of the release of EMVs harbouring specific GPI-anchored proteins, transcripts and microRNAs from rat and human adipocytes by histone H3 methylation at lysines 4 and 9 in interdependent fashion. Thus the EMV-mediated transfer of lipogenic and anti-lipolytic information between large and small adipocytes in response to certain physiological and pharmacological stimuli seems to be controlled by epigenetic mechanisms. Rat SVCs were prepared by collagenase (250 units/ml, type II, Worthington, St Katharinen, Germany) digestion (1 h, 37˚C) of epididymal fat pads (~5 g pieces) isolated [77] Salti, I. (2009) Efficacy and safety of insulin glargine and glimepiride in subjects with type 2 diabetes before, during and after the period of fasting in Ramadan. Diabetes
doi:10.4236/ajmb.2012.23020 fatcat:qdjigobyb5bx7fvvgpx4jbddbe