Effect of hypoxia and aging on PKC delta-mediated SC-35 phosphorylation in rat myocardial tissue.
Nuclear speckles, which are sites of pre-mRNA splicing and/or assembly components, are diffusely distributed throughout the nucleoplasm. They are composed of splicing factors (SFs), including SC-35, which are nuclear proteins that remove introns (noncoding sequences in the genes) from precursor mRNA molecules, to form mature RNA, which will be transported to the cytoplasm, site of protein synthesis and activation. In light of such evidences, here we report that hypoxia modulates in vivo SC-35 SF phosphorylation via protein kinase C (PKC) delta in young rat heart. Trichrome Mallory staining and TUNEL analysis along with immunohistochemistry and Western blotting have been performed on left ventricles excised from young and old rats exposed to intermittent hypoxia. Although young hypoxic myocardial cells appear smaller than normoxic cells, connective and endothelial components increase, SC-35 phosphorylation is particularly evident in the endothelium and paralleled by an increased expression of vascular endothelial growth factor (VEGF). In addition, SC-35 and PKC delta coimmunoprecipitation occurs, suggesting that SC-35 phosphorylation could be PKC delta-mediated and that hypoxic young heart needs to counteract the damage through a process of neoangiogenesis involving such SF. Even though the levels of SC-35 and PKC delta are high, the similar response disclosed by normoxic and hypoxic old rat hearts (both showing a fibrotic organization, similar endothelial components and VEGF levels) could be due to the existence of an impaired oxygen sensing mechanism and thus to a low rate of angiogenesis.
Cataldi
Amelia
A
Cattedra di Anatomia Umana, Facoltà di Farmacia, Università G. d'Annunzio, Chieti-Pescara, Chieti, Italy. cataldi@unich.its
Zingariello
Maria
M
Rapino
Monica
M
Zara
Susi
S
Daniele
Franca
F
Di Giulio
Camillo
C
Antonucci
Adriano
A
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D009687:Nuclear Proteins; C541456:Srsf2 protein, rat; D051745:Protein Kinase C-delta