Impaired voltage‐gated K+ channel expression in brain during experimental cancer cachexia

FEBS Letters

López-Soriano, Francisco J²  Tamkun, Michael M¹  Coma, Mireia²  Felipe, Antonio²  Carbó, Neus²  Argilés, Josep M²  Busquets, Silvia²  Vicente, Rubén² 

[1] Department of Physiology and Pharmacology, Colorado State University, Fort Collins, CO, USA;Molecular Physiology Laboratory, Departament de Bioquı́mica i Biologia Molecular, Universitat de Barcelona, Avda. Diagonal 645, E-08028 Barcelona, Spain

关键词: Potassium channel;    Cancer cachexia;    Apoptosis;    Brain;    Anorexia;   

DOI  :  10.1016/S0014-5793(03)00009-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 TNFα 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.

【 授权许可】

Unknown