The expression of the mitochondrial gene MT-ND4 is downregulated in cystic fibrosis.
Cystic fibrosis (CF) is a disease produced by mutations in the CFTR channel. We have previously reported that the CFTR chloride transport activity indirectly regulates the differential expression of several genes, including SRC and MUC1. Here we report that MT-ND4, a mitochondrial gene encoding a subunit of the mitochondrial Complex I (mtCx-I), is also a CFTR-dependent gene. A reduced expression of MT-ND4 was observed in CFDE cells (derived from a CF patient) when compared to CFDE cells ectopically expressing wild-type CFTR. The differential expression of MT-ND4 in CF was confirmed by RT-PCR. In situ hybridizations of deparaffinized human lung tissue slices derived from wt-CFTR or CF patients also showed downregulation of ND4 in CF. In addition, the CFTR chloride transport inhibitors glibenclamide and CFTR(inh)-172 also reduced MT-ND4 expression in CFDE cells ectopically expressing wt CFTR. These results suggest that the CFTR chloride transport activity indirectly up-regulates MT-ND4 expression.
Valdivieso
Angel G
AG
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Marcucci
Florencia
F
Taminelli
Guillermo
G
Guerrico
Anatilde González
AG
Alvarez
Sergio
S
Teiber
María Luz
ML
Dankert
Marcelo A
MA
Santa-Coloma
Tomás A
TA
D001483:Base Sequence; D001565:Benzoates / Q000494:pharmacology; D002460:Cell Line; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000235:genetics*; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D017403:In Situ Hybridization; D008168:Lung / Q000378:metabolism; D008969:Molecular Sequence Data; D009245:NADH Dehydrogenase / Q000235:genetics*; D053778:Thiazolidines / Q000494:pharmacology
C482900:3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone; D001565:Benzoates; C505032:CFTR protein, human; C098483:NADH dehydrogenase subunit 4; D053778:Thiazolidines; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D009245:NADH Dehydrogenase; D005905:Glyburide