Impaired voltage-gated K+ channel expression in brain during experimental cancer cachexia.
Cancer-induced cachexia affects most advanced cancer patients. It is characterized by anorexia, profound metabolic dysfunctions, and severe neurological disorders. Here we show that voltage-gated potassium channel (Kv) expression is impaired in the brain of tumor-bearing animals. Expression of both delayed rectifier (Kv1.1, Kv1.2, Kv1.3, Kv1.5, Kv1.6, Kv2.1, Kv3.1, Kv4.2) and A-type potassium channels (Kv1.4, Kv3.3, Kv3.4) was greatly down-regulated in brain from animals bearing a Yoshida AH-130 ascites hepatoma. The possible compensatory mechanisms (Kv1.4/Kv4.2), expression of redundant genes (Kv3.1/Kv3.3) and heteromultimeric channel formation (Kv2.1/Kv9.3) were also affected. The high circulating levels of TNFalpha and the reduced expression of the anti-apoptotic protein Bcl-XL found in the brain of tumor-bearing animals indicate that this response could be mediated by an increase in brain cell death due to apoptosis. The results suggest that brain function is impaired during cancer cachexia, and may account for the cancer-induced anorectic response and other neurological alterations.
Coma
Mireia
M
Molecular Physiology Laboratory, Departament de Bioqui;mica i Biologia Molecular, Universitat de Barcelona, Avda. Diagonal 645, E-08028 Barcelona, Spain.
Vicente
Rubén
R
Busquets
Silvia
S
Carbó
Neus
N
Tamkun
Michael M
MM
López-Soriano
Francisco J
FJ
Argilés
Josep M
JM
Felipe
Antonio
A
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002100:Cachexia / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D051668:Delayed Rectifier Potassium Channels; D005260:Female; D009374:Neoplasms, Experimental / Q000150:complications*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D051669:Shab Potassium Channels; D014158:Transcription, Genetic; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D051668:Delayed Rectifier Potassium Channels; C496991:Kcnb1 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein