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Role of ENaC/Degenerin Family in Glioblastoma Multiforme
Author(s) -
Kapoor Niren,
Fuller Catherine,
Benos Dale
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a536-c
Subject(s) - epithelial sodium channel , glioma , amiloride , acid sensing ion channel , sodium channel , chemistry , ion channel , patch clamp , cancer research , electrophysiology , biology , medicine , sodium , biochemistry , receptor , organic chemistry
Glioblastoma multiforme (GBM) is one of the most aggressive of the primary brain tumors. High‐grade gliomas express different subunits of the Epithelial Sodium Channel (ENaC)/Degenerin (Deg) family ( Berdiev et al., J. Biol. Chem., 278: 15023, 2003 ), characteristically displaying a basally active, amiloride‐sensitive cation current not seen in normal astrocytes or low‐grade gliomas. We hypothesize that this glioma current is due to a unique mixture of ENaC and ASIC subunits. Knocking down ASIC1 in U251‐MG glioma cells reduced the current by 60–70% in whole cell patch clamp recordings. ASIC1 protein expression was knocked down approximately 40–50% in these siRNA experiments as assessed by densitometry scanning. We have previously shown that γENaC co‐immunoprecipitates with both ASIC1 and ASIC2 in glioma cells ( Berdiev et al. ibid .) and may contribute to the glioma channel. To probe this interaction further, we have designed siRNA against γ‐ENaC, and have generated dominant negative mutations (I41X and S155X), for human β and γ‐ENaC, respectively as shown by Jernigan et al., Am. J. Physiol. 291: F118, 2006 . We are in the process of generating stable glioma cell lines with ASIC1, ASIC2, and γENaC subunits knocked down. This study aims to assess the role of these different ENaC/Deg subunits in glioma biology and to probe the composition of these novel ENaC/Deg heteromers. This study was supported by NIH Grant CA101952.