Doubts concerning functional endothelial nitric oxide synthase in human erythrocytes.

نویسندگان

  • Anke Böhmer
  • Bibiana Beckmann
  • Jörg Sandmann
  • Dimitrios Tsikas
چکیده

reason that Schoenwaelder and Jackson did not observe an increase in cytosolic free calcium at higher concentrations of ABT-263 is unclear but may well relate to differences such as higher platelet density (3 108 cells/mL used by them compared with the lower cell density 5 107 cells/mL used in our study).3 In this regard we have previously reported that the efficacy of both ABT-263 (Navitoclax) and ABT-737 in inducing apoptosis of primary chronic lymphocytic leukemic (CLL) cells is markedly diminished both by increasing cell density as well as by protein binding.4 Schoenwaelder and Jackson assessed the calcium response after only 10 minutes of pretreatment with ABT-737. In our initial study,3 the depletion of cellular calcium stores was assessed only after exposure to ABT-263 or ABT-737 for 2 hours. This time point was selected because we did not consistently detect caspase activation earlier and wished to investigate the contribution of caspases to the depletion of intracellular calcium stores. We can only hypothesize that 10 minutes of treatment with ABT-737 is not sufficient to deplete the intracellular calcium stores, thus explaining the obvious difference in our results. Taken together, our data consistently show that the BH3 mimetics, ABT-263 and ABT-737, can modulate the cellular calcium homeostasis in platelets. Further studies will be needed to address the functional consequences of this calcium response in vivo and its contribution to the thrombocypathy observed on ABT-263 administration.

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

EXPRESSION OF INDUCIBLE NITRIC OXIDE SYNTHASE GENE (iNOS) STIMULATED BY HYDROGEN PEROXIDE IN HUMAN ENDOTHELIAL CELLS

Inducible nitric oxide synthase (iNOS) gene expresses a calcium calmudolin-independent enzyme which can catalyse NO production from L-arginine. The induction of iNOS activity has been demonstrated in a wide variety of cell types under stimulation with cytokines and lipopoly saccharide (LPS). Previous studies indicated that all nitric oxide synthases (NOS) activated in human umbilical vein endot...

متن کامل

Association between T-786C polymorphism of endothelial nitric oxide synthase gene and level of the vessel dilation factor in patients with coronary artery disease

Various polymorphisms on endothelial nitric oxide synthase (eNOs) gene cause reduced production of NO, the endothelial relaxing factor, and may accelerate the process of atherosclerosis. The study designed to investigate the frequency of T-786C polymorphism of the eNOs gene in patients suffering from coronary artery disease (CAD) in north-west of Iran. One hundred twenty subjects including 60 p...

متن کامل

P-235: No Association of Endothelial Nitric Oxide Synthase (eNOS) -786T/C Polymorphism with Unexplained Recurrent Abortion in Iranian Women

Background: This is a case-control study to determine the relationship between endothelial nitric oxide synthase (eNOS) gene -786T/C polymorphism in women with unexplaiend recurrent abortion in comparison with healty women.Materials and Methods: 95 women with history of at least 2 unexplaiend recurrent abortion in the reproductive age range 20-35 years as patients group and 95 healty women (age...

متن کامل

Computational Prediction of the Effects of Single Nucleotide Polymorphisms of the Gene Encoding Human Endothelial Nitric Oxide Synthase

ABSTRACT           Background and Objective: Genetic variations in the gene encoding endothelial nitric oxide synthase (eNOS) enzyme affect the susceptibility to cardiovascular disease. Identification of the way these changes affect eNOS structure and function in laboratory conditions is difficult and time-consuming. Thus, it seems essential to ...

متن کامل

Spironolactone Inhibits NADPH Oxidase-Mediated Oxidative Stress and Dysregulation of the Endothelial NO Synthase in Human Endothelial Cells

Accumulating evidence indicates that aldosterone plays a critical role in the mediation of oxidative stress and vascular damage. NADPH oxidase has been recognized as a major source of oxidative stress in vasculature. However, the relation between NADPH oxidase in aldosterone-mediated oxidative stress in endothelial cells remains to be ascertained. The present study aimed to investigate the rel...

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:
  • Blood

دوره 119 5  شماره 

صفحات  -

تاریخ انتشار 2012