Amyloid-beta precursor protein expression and modulation in human embryonic stem cells: a novel role for human chorionic gonadotropin.
The amyloid-beta precursor protein (AbetaPP) is a ubiquitously expressed adhesion and neuritogenic protein whose processing has previously been shown to be regulated by reproductive hormones including the gonadotropin luteinizing hormone (LH) in human neuroblastoma cells. We report for the first time the expression of AbetaPP in human embryonic stem (hES) cells at the mRNA and protein levels. Using N- and C-terminal antibodies against AbetaPP, we detected both the mature and immature forms of AbetaPP as well as truncated variants ( approximately 53kDa, 47kDa, and 29kDa) by immunoblot analyses. Expression of AbetaPP is regulated by both the stemness of the cells and pregnancy-associated hormones. Addition of human chorionic gonadotropin, the fetal equivalent of LH that is dramatically elevated during pregnancy, markedly increased the expression of all AbetaPP forms. These results indicate a critical molecular signaling link between the hormonal environment of pregnancy and the expression of AbetaPP in hES cells that is suggestive of an important function for this protein during early human embryogenesis prior to the formation of neural precursor cells.
Porayette
Prashob
P
Section of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin and Geriatric Research, Education and Clinical Center, Veterans Administration Hospital, Madison, WI 53705, USA.
Gallego
Miguel J
MJ
Kaltcheva
Maria M
MM
Meethal
Sivan Vadakkadath
SV
Atwood
Craig S
CS
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D047108:Embryonic Development / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans
D016564:Amyloid beta-Protein Precursor; D006063:Chorionic Gonadotropin