- R. Heidstra (1)
- A.P. Mahonen (1)
- J. Meijerink (1)
- P. Plastina (1)
- M.C.R. Poland (1)
- B. Scheres (1)
- K. Tusscher ten (1)
- J.P. Vincken (1)
- R.F. Witkamp (1)
PLETHORA gradient formation mechanism separates auxin responses
Mahonen, A.P. ; Tusscher, K. ten; Diaz Trivino, S. ; Heidstra, R. ; Scheres, B. - \ 2014
Nature 515 (2014). - ISSN 0028-0836 - p. 125 - 129.
monocyte chemoattractant protein-1 - inflammatory breast-cancer - arabidopsis root apex - stem-cell niche - transcription factors - genomics browser - carcinoma cells - tumor - angiogenesis - expression
During plant growth, dividing cells in meristems must coordinate transitions from division to expansion and differentiation, thus generating three distinct developmental zones: the meristem, elongation zone and differentiation zone1. Simultaneously, plants display tropisms, rapid adjustments of their direction of growth to adapt to environmental conditions. It is unclear how stable zonation is maintained during transient adjustments in growth direction. In Arabidopsis roots, many aspects of zonation are controlled by the phytohormone auxin and auxin-induced PLETHORA (PLT) transcription factors, both of which display a graded distribution with a maximum near the root tip2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. In addition, auxin is also pivotal for tropic responses13, 14. Here, using an iterative experimental and computational approach, we show how an interplay between auxin and PLTs controls zonation and gravitropism. We find that the PLT gradient is not a direct, proportionate readout of the auxin gradient. Rather, prolonged high auxin levels generate a narrow PLT transcription domain from which a gradient of PLT protein is subsequently generated through slow growth dilution and cell-to-cell movement. The resulting PLT levels define the location of developmental zones. In addition to slowly promoting PLT transcription, auxin also rapidly influences division, expansion and differentiation rates. We demonstrate how this specific regulatory design in which auxin cooperates with PLTs through different mechanisms and on different timescales enables both the fast tropic environmental responses and stable zonation dynamics necessary for coordinated cell differentiation.
The ethanolamide metabolite of DHA, docosahexaenoylethanolamine, shows immunomodulating effects in mouse peritoneal and RAW264.7 macrophages: evidence for a new link between fish oil and inflammation
Meijerink, J. ; Plastina, P. ; Vincken, J.P. ; Poland, M.C.R. ; Attya, M. ; Balvers, M.G.J. ; Gruppen, H. ; Gabriele, B. ; Witkamp, R.F. - \ 2011
British Journal of Nutrition 105 (2011)12. - ISSN 0007-1145 - p. 1798 - 1807.
nitric-oxide synthase - monocyte chemoattractant protein-1 - fatty-acid-composition - docosahexaenoic acid - n-acylethanolamine - insulin-resistance - adipose-tissue - reduces atherosclerosis - eicosapentaenoic acid - dietary-fat
Several mechanisms have been proposed for the positive health effects associated with dietary consumption of long-chain n-3 PUFA (n-3 LC-PUFA) including DHA (22 : 6n-3) and EPA (20 : 5n-3). After dietary intake, LC-PUFA are incorporated into membranes and can be converted to their corresponding N-acylethanolamines (NAE). However, little is known on the biological role of these metabolites. In the present study, we tested a series of unsaturated NAE on the lipopolysaccharide (LPS)-induced NO production in RAW264.7 macrophages. Among the compounds tested, docosahexaenoylethanolamine (DHEA), the ethanolamide of DHA, was found to be the most potent inhibitor, inducing a dose-dependent inhibition of NO release. Immune-modulating properties of DHEA were further studied in the same cell line, demonstrating that DHEA significantly suppressed the production of monocyte chemotactic protein-1 (MCP-1), a cytokine playing a pivotal role in chronic inflammation. In LPS-stimulated mouse peritoneal macrophages, DHEA also reduced MCP-1 and NO production. Furthermore, inhibition was also found to take place at a transcriptional level, as gene expression of MCP-1 and inducible NO synthase was inhibited by DHEA. To summarise, in the present study, we showed that DHEA, a DHA-derived NAE metabolite, modulates inflammation by reducing MCP-1 and NO production and expression. These results provide new leads in molecular mechanisms by which DHA can modulate inflammatory processes.