Username


Password

Forgot Password?

Preview

Sign-in free and Explore the Exciting World of BiomedExperts:
  • Over 1,800,000 Profiles
  • More than 3,500 Organizations worldwide
  • State of the Art Network Visualizations
  • Manage your own Profile
  • Locate Experts in your Country/Region
  • Locate Experts in your 1. and 2. Level Network
  • Connect to Experts Worldwide

find experts for

Sign-in to see more
2009: López J J; Redondo P C; Salido G M; Pariente J A; Rosado J A
N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine induces apoptosis through the activation of caspases-3 and -8 in human platelets. A role for endoplasmic reticulum stress.
Journal of thrombosis and haemostasis : JTH 2009;7(6):992-9.
BACKGROUND: Apoptosis or programmed cell death involves a number of biochemical events, including the activation of caspases, which lead to specific cell morphology changes and ultimately cell death. Traditionally, two apoptotic pathways have been described: the cell-surface death receptor-dependent extrinsic pathway and the mitochondria-dependent intrinsic pathway. Alternatively, apoptosis has been reported to be induced by endoplasmic reticulum (ER) stress, which is mainly induced by a reduction in intraluminal free Ca(2+) concentration ([Ca(2+)](ER)). OBJECTIVES: The present study aimed to investigate the development of apoptotic events after ER stress induced by N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), an ER Ca(2+) chelator, in human platelets. METHODS: Changes in cytosolic free Ca(2+) concentration, caspase activity and phosphatidylserine externalization were determined by fluorimetric techniques. RESULTS: Our results indicate that TPEN reduces the amount of free Ca(2+) releasable by the Ca(2+)-mobilizing agonist thrombin. TPEN induced activation of caspase-3, -8 and -9 and subsequent phosphatidylserine externalization. The ability of TPEN to induce phosphatidylserine externalization was smaller than that of thrombin. In addition, TPEN was able to induce phosphorylation of the eukaryotic initiation factor 2 alpha (eIF2 alpha). TPEN-mediated caspase-3 activation requires functional caspase-8, but is independent of H(2)O(2) generation. Activation of caspase-3 and -8 by TPEN was prevented by salubrinal, an agent that prevents ER stress-induced apoptosis. CONCLUSION: These findings provide experimental evidence for the existence of ER stress-mediated apoptosis in human platelets, a process that might limit platelet life span upon prolonged stimulation with agonists.

Post to CiteULike

Sign in free and see...

Visualized networks:
See your personal network in
sophisticated graphical views
GeoTargeted Searches:
Locate experts around the world
and connect with global collaborators
Research Profiles:
See the visualized research activity
of experts around the globe
Sign-in to see more