Effect of chromium on apolipoprotein A-I expression in HepG2 cells.
OBJECTIVE
Chromium is a key micronutrient required for lipid and carbohydrate metabolism. Some but not all clinical trials have associated use of chromium supplements with improved insulin sensitivity and lipid profile including increased high-density lipoprotein cholesterol levels.


METHODS
Because apolipoprotein A-I (apoA-I) is the principal protein of high-density lipoprotein, the molecular pathways underlying chromium-related changes in apoA-I expression were studied in a human hepatoma cell line (HepG2) transfected with full-length apoA-I promoter attached to the reporter chloramphenicol acetyl transferase gene.


RESULTS
Exposure of these cells to different concentrations of chromium chloride (0, 0.5, 1.0, and 3.0 mM) resulted in a dose-dependent decrease in apoA-I promoter activity (chloramphenicol acetyl transferase activity expressed as a percentage of an internal control was 99.4 +/- 7.2% in control cells versus 87.6 +/- 5.0%, 73.4 +/- 2.3%, and 36.6 +/- 3.9%, respectively, P < 0.01). Chromium chloride at 10 mM concentration was toxic and caused death in a large number of cells. Treating HepG2 cells with other minerals known to have insulin-sensitizing effects such as magnesium (1 mM), zinc (0.2 mM), and vanadyl sulfate (0.1 mM) significantly reduced apoA-I promoter activity in the presence and absence of 100 microU/mL of insulin. Northern blot analyses showed that the apoA-I mRNA content of cells treated with 0.2 mM of chromium chloride relative to G3PDH mRNA was not significantly increased compared with controls (0.652 +/- 0.122 versus 0.745 +/- 0.143, the ratio of apoA-I to glyceraldehyde 3-phosphate dehydrogenase (G3PDH) mRNA in control and chromium-treated cells, respectively). Western blot analyses of proteins secreted in culture media indicated that neither chromium treatment of the HepG2 cells (858.0 +/- 151.4 arbitrary units) nor treatment with magnesium (1323.3 +/- 175.7) or vanadium (1102 +/- 78.7) significantly altered apoA-I concentrations compared with controls (1061.7 +/- 114.7). However treatment of HepG2 cells with 0.2 mM of zinc significantly reduced apoA-I concentrations (291.0 +/- 29.2 versus 1061.7 +/- 114.7; P < 0.001).


CONCLUSIONS
Supraphysiologic concentrations of chromium and other minerals with known insulin-sensitizing activity may reduce apoA-I promoter activity in cultured cells. Whether similar changes may occur in vivo remains to be shown. However, these observations do not support the use of pharmacologic amounts of chromium supplementation to enhance the cardioprotective lipid profile.
Haas
Michael J
MJ
Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, Missouri, USA.
Sawaf
Randa
R
Horani
Mohamad H
MH
Gobal
Freij
F
Wong
Norman C W
NC
Mooradian
Arshag D
AD
D000975:Antioxidants / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology*; D017608:Chromium Compounds / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D008075:Lipoproteins, HDL; D008113:Liver Neoplasms; D008274:Magnesium / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
D000975:Antioxidants; D016632:Apolipoprotein A-I; D002712:Chlorides; D017608:Chromium Compounds; D007328:Insulin; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D014638:Vanadates; C017133:chromous chloride; D015500:Chloramphenicol O-Acetyltransferase; D008274:Magnesium; D015032:Zinc