Hypertension and nephrology

[Changes in endothelial cells caused by cigarette smoke]

WAGNER László1, LACZY Boglárka1, CSEH Judit1, TAMASKÓ Mónika1, MAZÁK István1, MARKÓ Lajos1, MOLNÁR Gergő Attila1, WAGNER Zoltán1, MOHÁS Márton1, FEKETE Andrea2, WITTMANN István1

JUNE 20, 2010

Hypertension and nephrology - 2010;14(03)

[Endothelial nitric oxide synthase enzyme is regulated through the phosphorylation of the Ser(1177) and the Thr(495) sites, which influence the biological availabilaty of nitric oxide. We examined the acute effect of cigarette smoke, which decreases nitric oxide production. Endothelial cells were treated with different concentrations and for different times with cigarette smoke buffer, then with reduced glutathione or different protein kinase inhibitors. We determined the total and the phosphorylated nitric oxide synthase levels with Western blot. Cigarette smoke increased phosphorylation in a concentration- and time dependent manner at the Ser(1177) site and more pronounced at the Thr(495) site. Besides, it also led to the dissociation of the active dimer form of the enzyme. Reduced glutathione inhibited these phosphorylations and prevented the dissociation of endothelial nitric oxide synthase enzyme. The inhibition of protein kinase A or B did not influence the effect of cigarette smoke. However, protein kinase C inhibitors increased the phosphorylation caused by cigarette smoke at Ser(1177), but decreased it at Thr(495) sites. Summarized, cigarette smoke shifts the phosphorylation of the enzyme towards an inhibitory state, further on, it leads to the dissociation of the enzymatically active form. This results in the decreased biological availabilaty of nitric oxide, in which protein kinase C may play an important role.]

AFFILIATIONS

  1. Pécsi Tudományegyetem, Általános Orvostudományi Kar, II. Sz. Belgyógyászati Klinika és Nephrológiai Centrum, Pécs
  2. Semmelweis Egyetem, I. Sz. Gyermekgyógyászati Klinika, Budapest

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