eNOS phosphorylation and translocation are altered in male but not female mice by increased activation of the Gαq protein.
Little is known about sex-dependent physiological and pathophysiological differences in cardiac endothelial nitric oxide synthase (eNOS) expression and activation. Therefore, we investigated cardiac morphology and eNOS protein expression, including its translocation-dependent activation and phosphorylation, in cardiac tissue of male and female wild-type mice and transgenic heart-failure mice having a cardiac-specific, 5-fold overexpression of the Galphaq protein. In addition, we measured calcineurin protein expression. Heart-to-body weight ratio was increased in Galphaq mice. Female wild-type mice showed higher eNOS protein expression and activation (translocation and phosphorylation) than did wild-type males. In cardiac tissue of Galphaq mice, these sex-dependent differences remained or were enhanced. Protein expression of the catalytic subunit calcineurin A, which has been shown to dephosphorylate eNOS, was higher in wild-type males than in wild-type females. These differences were increased in the Galphaq mice model. We conclude that sex differences exist in cardiac eNOS protein expression and phosphorylation. Increased activation of the Galphaq protein appears to alter eNOS protein expression and phosphorylation only in males.
Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Cologne 50933, Germany.
C
C
Ruiz-Holst
B
B
Bölck
A
A
Ghanem
K
K
Tiemann
S
S
Brokat
V
V
Regitz-Zagrosek
W
W
Bloch
Robert H G
RH
Schwinger
K
K
Brixius
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006333:Heart Failure / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D012727:Sex Characteristics
D052250:Nitric Oxide Synthase Type III; D043802:GTP-Binding Protein alpha Subunits, Gq-G11