Lysophosphatidylcholine-induced apoptosis in H19-7 hippocampal progenitor cells is enhanced by the upregulation of Fas Ligand.
Lysophospholipids regulate a wide array of biological processes including apoptosis and neutrophil migration. Fas/Apo-1 and its ligand (FasL) participate in neuronal cell apoptosis causing various neurological diseases. Here, we use hippocampal neuroprogenitor cells to investigate how lysophosphatidylcholine (LPC) induces apoptosis in H19-7 hippocampal progenitor cells via Fas/Fas ligand-mediated apoptotic signaling pathway. Exposed cells with LPC presented on apoptotic morphology, positive TUNEL staining, and DNA fragmentation. We found that the expression of FasL was increased after LPC treatment. Furthermore, LPC-induced H19-7 cell apoptosis was decreased by agonistic anti-FasL antibody. In addition to promotion of caspase cascade activity by LPC, the administration of the caspase inhibitor, DEVD-fmk, prevented H19-7 cell apoptosis. LPC also increased the activation of nuclear factor-kappaB (NF-kappaB), which in turn, significantly increased FasL mRNA level. The increase in FasL mRNA level by NF-kappaB transfection was significantly decreased in the presence of IkappaB-SR, a super-repressor of IkappaB. Taken together, these results demonstrate that LPC has the ability to induce apoptosis in H19-7 cells through the upregulation of FasL expression via NF-kappaB activation.
Sun
Yuanjie
Y
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chunchon, Kangwon-do, 200-702, South Korea.
Lee
Joo-Hyun
JH
Kim
Nam-Ho
NH
Lee
Chang-Wook
CW
Kim
Min-Ju
MJ
Kim
Seung-Hyuk
SH
Huh
Sung-Oh
SO
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000502:physiology; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D053222:Fas Ligand Protein; C115270:G2A receptor; D008244:Lysophosphatidylcholines; D016328:NF-kappa B; D043562:Receptors, G-Protein-Coupled; D020169:Caspases