Cachexia induced by Walker 256 tumor growth causes rat lymphocyte death.
Death induction by Walker 256 tumor cachexia in non-tumor-infiltrating lymphocytes was investigated. Lymphocytes from cachectic tumor-bearing rats presented a higher proportion of cells with ruptured membranes, indicating necrotic cell death. The cachexia induced by Walker 256 tumor also increased by 3.6-fold the percentage of cells with fragmented DNA, suggestive of apoptotic cell death. The mitochondria involvement was examined by analysis of mitochondria transmembrane potential using rhodamine 123. Lymphocytes from cachectic tumor-bearing rats presented a more pronounced depolarization of mitochondrial transmembrane potential in comparison with cells from the control group. The expression of important proapoptotic (Bcl-xs, Bax, p53, caspase-3) and antiapoptotic genes (Bcl-2 and Bcl-xL) was also altered by tumor cachexia. These results suggest that the immunosuppression induced by Walker 256 tumor cachexia is at least in part a result of lymphocyte death. Evidence was found for the involvement of mitochondria and important proapoptotic genes in the process of lymphocyte death by Walker 256 tumor cachexia.
de Lima
Thais Martins
TM
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Cidade Universitária, Av. Professor Lineu Prestes 1524, 05508-900, São Paulo, Brazil.
Lima
Manuela M Ramos
MM
Almeida
Débora C G
DC
Mendonça
José Roberto
JR
Curi
Rui
R
D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D002100:Cachexia / Q000209:etiology*; D002279:Carcinoma 256, Walker / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008564:Membrane Potentials; D008928:Mitochondria; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured / Q000637:transplantation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases