Differential gene expression in intestinal epithelial cells induced by single and mixtures of potato glycoalkaloids.
Alpha-chaconine and alpha-solanine are naturally occurring toxins. They account for 95% of the total glycoalkaloids in potatoes ( Solanum tuberosum L.). At high levels, these glycoalkaloids may be toxic to humans, mainly by disrupting cell membranes of the gastrointestinal tract. Gene-profiling experiments were performed, whereby Caco-2 cells were exposed to equivalent concentrations (10 microM) of pure alpha-chaconine or alpha-solanine or glycoalkaloid mixtures of varying alpha-chaconine/alpha-solanine ratios for 6 h. In addition, lactate dehydrogenase, cell cycle, and apoptosis analyses experiments were also conducted to further elucidate the effects of glycoalkaloids. The main aims of the study were to determine the transcriptional effects of these glycoalkaloid treatments on Caco-2 cells and to investigate DNA microarray utility in conjunction with conventional toxicology in screening for potential toxicities and their severity. Gene expression and pathway analyses identified changes related to cholesterol biosynthesis, growth signaling, lipid and amino acid metabolism, mitogen-activated protein kinase (MAPK) and NF-kappaB cascades, cell cycle, and cell death/apoptosis. To varying extents, DNA microarrays discriminated the severity of the effect among the different glycoalkaloid treatments.
Mandimika
Tafadzwa
T
RIKILT, Institute of Food Safety, Wageningen University and Research Centre, The Netherlands.
Baykus
Hakan
H
Vissers
Yvonne
Y
Jeurink
Prescilla
P
Poortman
Jenneke
J
Garza
Cutberto
C
Kuiper
Harry
H
Peijnenburg
Ad
A
D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002784:Cholesterol / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000378:metabolism; D012720:Severity of Illness Index; D012992:Solanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology*; D011198:Solanum tuberosum / Q000737:chemistry*
D011506:Proteins; D012992:Solanine; C011860:alpha-chaconine; D002784:Cholesterol; D007770:L-Lactate Dehydrogenase