Proteomics and gene expression analyses of squalene-supplemented mice identify microsomal thioredoxin domain-containing protein 5 changes associated with hepatic steatosis.
Squalene is an abundant hydrocarbon present in virgin olive oil. Previous studies showed that its administration decreased atherosclerosis and steatosis in male apoE-knock-out mice. To study its effects on microsomal proteins, 1g/kg/day of squalene was administered to those mice. After 10 weeks, hepatic fat content was assessed and protein extracts of microsomal enriched fractions from control and squalene-treated animals were analyzed by 2D-DIGE. Spots exhibiting significant differences were identified by peptide fingerprinting and MSMS analysis. Squalene administration modified the expression of thirty-one proteins involved in different metabolic functions and increased the levels of those involved in vesicle transport, protein folding and redox status. Only mRNA levels of 9 genes (Arg1, Atp5b, Cat, Hyou1, Nipsnap1, Pcca, Pcx, Pyroxd2, and Txndc5) paralleled these findings. No such mRNA changes were observed in wild-type mice receiving squalene. Thioredoxin domain-containing protein 5 (TXNDC5) protein and mRNA levels were significantly associated with hepatic fat content in apoE-ko mice. These results suggest that squalene action may be executed through a complex regulation of microsomal proteins, both at the mRNA and post-transcriptional levels and the presence of apoE may change the outcome. Txndc5 reflects the anti-steatotic properties of squalene and the sensitivity to lipid accumulation.
Departamento Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, Spain.
Adela
A
Ramírez-Torres
Sílvia
S
Barceló-Batllori
Roberto
R
Martínez-Beamonte
María A
MA
Navarro
Joaquín C
JC
Surra
Carmen
C
Arnal
Natalia
N
Guillén
Sergio
S
Acín
Jesús
J
Osada
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008862:Microsomes, Liver / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013185:Squalene / Q000494:pharmacology*; D013879:Thioredoxins / Q000096:biosynthesis* / Q000235:genetics
D001057:Apolipoproteins E; C482592:PC-TRP protein, mouse; D012333:RNA, Messenger; D013879:Thioredoxins; D013185:Squalene