Induction of apoptosis in bone marrow cells by gangliosides produced by a T cell lymphoma.
The present study was conducted to investigate the mode of cell death of bone marrow cells (BMC) treated in vivo or in vitro with gangliosides (DLG) derived from a T cell lymphoma, designated as Dalton's lymphoma (DL). BMC undergoing cell death showed morphological features characteristic to apoptosis such as cell shrinkage, plasma membrane blebbing and densely stained chromatin. DLG-induced apoptosis was further confirmed by analysis of DNA from DLG-treated BMC by flow cytometry and agarose gel electrophoresis which showed an increase in hypodiploid DNA and internucleosomal DNA cleavage, respectively. Immunoblotting of p53 and Bax demonstrated an increase in the levels of p53 and Bax proteins. BMC treated with DLG also showed translocation of NF-kappaB protein into the nucleus. Antibodies to ganglioside G(D3), a constituent of DLG, neutralized the effect of DLG. Further, supplementation of DLG-containing BMC cultures with granulocyte macrophage-colony stimulating factor (GM-CSF) or macrophage-colony stimulating factor (M-CSF) prevented the apoptosis-inducing action of DLG.
Bharti
A C
AC
School of Biotechnology, Banaras Hindu University, Varanasi, India.
Singh
S M
SM
D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005732:Gangliosides / Q000378:metabolism* / Q000494:pharmacology*; D005856:Germ-Free Life; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis; D016399:Lymphoma, T-Cell / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D005732:Gangliosides; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor