Heterogeneous activation of p19Arf in pulmonary artery smooth muscle cells.

نویسندگان

  • Victor Solodushko
  • Diego F Alvarez
  • Ryan Viator
  • Tiffany Messerall
  • Brian Fouty
چکیده

p19(ARF) is a tumor suppressor that leads to cell cycle arrest or apoptosis by stabilizing p53. p19(ARF) is not critical for cell cycle regulation under normal conditions, but loss of p19(ARF) is seen in many human cancers, and a murine p19(Arf) knockout model leads to malignant proliferation and tumor formation; its role in controlling nonmalignant proliferation is less defined. To examine this question, pulmonary artery smooth muscle cells (PASMC) were expanded in culture from a transgenic mouse in which the coding sequence of the p19(Arf) gene was replaced with a cDNA encoding green fluorescent protein (GFP), leaving the promoter intact. During the first 10 days in culture, wild-type, heterozygous, and knockout PASMC grew similarly, but, by day 14, p19(Arf)-deficient PASMC proliferated faster than p19(Arf) heterozygous or wild-type cells; reexpression of p19(Arf) prevented the increased proliferation. This time course correlated with activation of the p19(Arf) promoter, as indicated by the appearance of GFP positivity in p19(Arf)-deficient PASMC. By day 42, ∼80% of p19(Arf)-deficient cells were GFP-positive. When GFP-positive, p19(Arf)-deficient cells were sorted and subcultured separately, they remained GFP-positive, indicating that once cells had activated the p19(Arf) promoter, the promoter remained active in those and all subsequent daughter cells. In contrast, GFP-negative p19(Arf)-deficient cells gave rise to a combination of GFP-positive and -negative daughter cells over time. These results suggest that a subpopulation of PASMC are resistant to the signals that activate the p19(Arf) promoter, an event that would normally target these cells for arrest or cell death.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Histological Study of the Elastic Artery, Muscular Artery, and Their Junction in Neonate Dog

Introduction: We did this study because there were a few studies about aorto-branch junction. Methods: Four light microscope and electron microscope study, the abdominal aorta, renal artery, and the adjoining right and left renal arteries were dissected out from 4 neonate dogs. Results: Based on the results, there is only one cell type in the tunica intima of endothelium in both art...

متن کامل

Heterogeneous activation of p19 in pulmonary artery smooth muscle cells

Solodushko V, Alvarez DF, Viator R, Messerall T, Fouty B. Heterogeneous activation of p19 in pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 300: L642–L647, 2011. First published January 7, 2011; doi:10.1152/ajplung.00117.2010.— p19 is a tumor suppressor that leads to cell cycle arrest or apoptosis by stabilizing p53. p19 is not critical for cell cycle regulation under ...

متن کامل

Heterogeneous gene expression and functional activity of ryanodine receptors in resistance and conduit pulmonary as well as mesenteric artery smooth muscle cells.

BACKGROUND Hypoxia causes heterogeneous contractile responses in resistance and conduit pulmonary as well as systemic (mesenteric) artery smooth muscle cells (RPASMCs, CPASMCs and MASMCs), but the underlying mechanisms are largely unknown. In this study, we aimed to investigate whether the gene expression and functional activity of ryanodine receptors (RyRs) would be different in these 3 cell t...

متن کامل

Mitochondrial transplantation attenuates hypoxic pulmonary vasoconstriction

Hypoxia triggers pulmonary vasoconstriction, however induces relaxation of systemic arteries such as femoral arteries. Mitochondria are functionally and structurally heterogeneous between different cell types. The aim of this study was to reveal whether mitochondrial heterogeneity controls the distinct responses of pulmonary versus systemic artery smooth muscle cells to hypoxia. Intact mitochon...

متن کامل

Oxygen-induced fetal pulmonary vasodilation is mediated by intracellular calcium activation of K(Ca) channels.

O(2) sensing in fetal pulmonary artery smooth muscle is critically important in the successful transition to air breathing at birth. However, the mechanism by which the fetal pulmonary vasculature senses and responds to an acute increase in O(2) tension is not known. Isolated fetal pulmonary artery smooth muscle cells were kept in primary culture for 5-14 days in a hypoxic environment (20-30 mm...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • American journal of physiology. Lung cellular and molecular physiology

دوره 300 4  شماره 

صفحات  -

تاریخ انتشار 2011