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Impaired voltage‐gated K + channel expression in brain during experimental cancer cachexia
Author(s) -
Coma Mireia,
Vicente Rubén,
Busquets Silvia,
Carbó Neus,
Tamkun Michael M,
López-Soriano Francisco J,
Argilés Josep M,
Felipe Antonio
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00009-7
Subject(s) - cachexia , potassium channel , cancer , endocrinology , medicine , apoptosis , cancer research , biology , neuroscience , biochemistry
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.