DYRK1A overexpression decreases plasma lecithin:cholesterol acyltransferase activity and apolipoprotein A-I levels.
OBJECTIVE
Down syndrome is caused by trisomy of all or part of human chromosome 21. Individuals with Down syndrome present some metabolic abnormalities involving lipoproteins, notably lower high-density lipoprotein levels associated with altered lecithin:cholesterol acyltransferase activity and apolipoprotein A-I levels. DYRK1A is a kinase overexpressed in Down syndrome that can activate the STAT3 pathway, which is involved in lecithin:cholesterol acyltransferase expression. Therefore, we characterized the role of DYRK1A overexpression on lecithin:cholesterol acyltransferase activity and expression in mouse models.


METHODS
Effects of Dyrk1a overexpression were examined in mice overexpressing Dyrk1a by ELISA, chemical analyses and Western blotting.


RESULTS
Overexpression of DYRK1A decreased plasma lecithin:cholesterol acyltransferase activity and hepatic STAT3 activation, which was associated with activation of SHP2, a tyrosine phosphatase. Although hepatic apolipoprotein E and D levels were increased in mice overexpressing DYRK1A, decreased plasma lecithin:cholesterol acyltransferase activity was associated with decreased hepatic and plasma apolipoprotein A-I levels. High-density lipoprotein-cholesterol levels were also decreased in plasma despite similar total cholesterol and non-high-density lipoprotein-cholesterol levels.


CONCLUSIONS
We identified the role of DYRK1A overexpression on altered lipoprotein metabolism.
Université Paris Diderot, Sorbonne Paris Cité, Unit of Functional and Adaptive Biology (BFA), EAC-CNRS 4413, Case 7104, 75205 Paris cedex 13, France.
Asma
A
Tlili
Christophe
C
Noll
Sandrine
S
Middendorp
Arnaud
A
Duchon
Marie
M
Jouan
Eva
E
Benabou
Yann
Y
Hérault
Jean-Louis
JL
Paul
Jean-Maurice
JM
Delabar
Nathalie
N
Janel
D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood*; D053399:Apolipoproteins D / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D004789:Enzyme Activation; D015870:Gene Expression; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000097603:Dyrk Kinases
D016632:Apolipoprotein A-I; D053399:Apolipoproteins D; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D017346:Protein Serine-Threonine Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D011505:Protein-Tyrosine Kinases; D050796:STAT3 Transcription Factor; D000097603:Dyrk Kinases
Apo; BAC; BSA; DS; DYRKs; Down syndrome; ES; HDL; HRP; HSA21; LCAT; Lipoprotein metabolism; Q-PCR; SHP2; STAT3; Tyrosine phosphorylation; apolipoprotein; bacterial artificial chromosome; bovine serum albumin; dual-specificity tyrosine-(Y)-phosphorylation regulated kinases; embryonic stem; high-density lipoprotein; horseradish peroxidase; human chromosome 21; lecithin:cholesterol acyltransferase; quantitative reverse-transcription polymerase chain reaction