PCR arrays identify metallothionein-3 as a highly hypoxia-inducible gene in human adipocytes.
Hypoxia-signalling pathway PCR arrays were used to examine the integrated response of human adipocytes to low O(2) tension. Incubation of adipocytes in 1% O(2) for 24h resulted in no change in the expression of 63 of the 84 genes on the arrays, a reduction in expression of 9 genes (including uncoupling protein 2) and increased expression of 12 genes. Substantial increases (>10-fold) in leptin, angiopoietin-like protein 4, VEGF and GLUT-1 mRNA levels were observed. The expression of one gene, metallothionein-3 (MT-3), was dramatically (>600-fold) and rapidly (by 60 min) increased by hypoxia. MT-3 gene expression was also substantially induced by hypoxia mimetics (CoCl(2), desferrioxamine, dimethyloxalylglycine), indicating transcriptional regulation through HIF-1. Hypoxia additionally induced MT-3 expression in preadipocytes, and MT-3 mRNA was detected in human (obese) subcutaneous and omental adipose tissue. MT-3 is a highly hypoxia-inducible gene in human adipocytes; the protein may protect adipocytes from hypoxic damage.
Wang
Bohan
B
Obesity Biology Unit, School of Clinical Sciences, University of Liverpool, Duncan Building, Liverpool L69 3GA, UK.
Wood
I Stuart
IS
Trayhurn
Paul
P
D017667:Adipocytes / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics*; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D046509:Tissue Culture Techniques
D051793:Hypoxia-Inducible Factor 1; D012333:RNA, Messenger; D008668:Metallothionein