TY - JOUR
T1 - Effect of HFE variants on sphingolipid expression by SH-SY5Y human neuroblastoma cells
AU - Ali-Rahmani, F.
AU - Hengst, J. A.
AU - Connor, J. R.
AU - Schengrund, C. L.
N1 - Funding Information:
Acknowledgments The authors thank Dr. Jong Yun for helpful discussions, Dr. K.A. Petro for her help with isolating lipid rafts, and Dr. Sang Lee for providing us with the SH-SY5Y cells stably transfected to express either FLAG-tagged WT-, H63Dor C282Y-HFE alleles. We also thank the Jake Gittlen Cancer Research Foundation (JAH), and the George M. Leader Family Corporation (JRC) for their support.
PY - 2011/9
Y1 - 2011/9
N2 - C282Y and H63D are two common variants of the hemochromatosis protein HFE. SH-SY5Y human neuroblastoma cells stably transfected to express either wild type HFE (WT-HFE), or the C282Y or H63D allele were analyzed for effect of expression of the mutant proteins on transcription of 14 enzymes involved in sphingolipid metabolism. Cells expressing the C282Y variant showed significant increases (>2-fold) in transcription of five genes and decreases in two compared to that seen for cells expressing WT-HFE, while cells expressing the H63D variant showed an elevation in transcription of one gene and a decrease in two. These changes were seen as alterations in ganglioside composition, cell surface binding by the binding subunit of cholera toxin, expression of sphingosine- kinase-1 and synthesis of sphingosine-1-phosphate. These changes may explain why C282Y-HFE is a risk factor for colon and breast cancer and possibly protective against Alzheimer's disease while H63D-HFE is a risk factor for neurodegenerative diseases.
AB - C282Y and H63D are two common variants of the hemochromatosis protein HFE. SH-SY5Y human neuroblastoma cells stably transfected to express either wild type HFE (WT-HFE), or the C282Y or H63D allele were analyzed for effect of expression of the mutant proteins on transcription of 14 enzymes involved in sphingolipid metabolism. Cells expressing the C282Y variant showed significant increases (>2-fold) in transcription of five genes and decreases in two compared to that seen for cells expressing WT-HFE, while cells expressing the H63D variant showed an elevation in transcription of one gene and a decrease in two. These changes were seen as alterations in ganglioside composition, cell surface binding by the binding subunit of cholera toxin, expression of sphingosine- kinase-1 and synthesis of sphingosine-1-phosphate. These changes may explain why C282Y-HFE is a risk factor for colon and breast cancer and possibly protective against Alzheimer's disease while H63D-HFE is a risk factor for neurodegenerative diseases.
UR - https://www.scopus.com/pages/publications/80755163525
UR - https://www.scopus.com/pages/publications/80755163525#tab=citedBy
U2 - 10.1007/s11064-011-0403-8
DO - 10.1007/s11064-011-0403-8
M3 - Article
C2 - 21243428
AN - SCOPUS:80755163525
SN - 0364-3190
VL - 36
SP - 1687
EP - 1696
JO - Neurochemical Research
JF - Neurochemical Research
IS - 9
ER -
