June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
KZ-41 prevents melphalan-induced intercellular adhesion molecule-1 (ICAM-1) upregulation and apoptosis in retinal endothelial cells
Author Affiliations & Notes
  • Qiuhua Zhang
    Ophthalmology, Univ of Tennessee Hlth Sci Ctr, Memphis, TN
  • Jordan Toutounchian
    Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN
  • Charles Yates
    Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN
  • Matthew Wilson
    Ophthalmology, Univ of Tennessee Hlth Sci Ctr, Memphis, TN
  • Jena Steinle
    Ophthalmology, Univ of Tennessee Hlth Sci Ctr, Memphis, TN
    Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN
  • Footnotes
    Commercial Relationships Qiuhua Zhang, None; Jordan Toutounchian, None; Charles Yates, RxBio, Inc (C), RxBio, Inc (P), RxBio, Inc (R); Matthew Wilson, None; Jena Steinle, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1259. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Qiuhua Zhang, Jordan Toutounchian, Charles Yates, Matthew Wilson, Jena Steinle; KZ-41 prevents melphalan-induced intercellular adhesion molecule-1 (ICAM-1) upregulation and apoptosis in retinal endothelial cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1259.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: To determine whether a novel NF-κB inhibitor, KZ-41, can inhibit melphalan’s actions on retinal endothelial cells (REC) inflammation and apoptosis, without eliminating the chemotherapeutic efficacy of melphalan on cell death of retinoblastoma cells (Y79).

Methods: REC were cultured in M131 medium supplemented with growth factors and antibiotics. Once cells reached confluence, they were treated with or without 10 μM KZ-41, following treatment with 4 μg/ml melphalan. Cell proteins were extracted and analyzed for intracellular adhesion molecule 1 (ICAM-1) levels and cell death ELISA. REC were also transfected with or without NF-κB siRNA before melphalan treatment to determine the involvement of NF-κB in REC apoptosis and ICAM-1 levels. Cell lysates were processed for ICAM-1 levels and cell death ELISA. Western blotting was done to verify NF-κB knockdown following both NF-κB siRNA transfection and KZ-41 treatment. Phospho-P38MAPK inhibitor was also treated before KZ-41 and melphalan treatment and cell lysates were tested for ICAM-1 levels and REC cell death. We also cultured retinoblastoma cells (Y79) in RMPI-1640 medium supplemented with 20% fetal bovine serum and antibiotics and performed a cell death ELISA after melphalan + KZ-41 treatment to verify that the treatments did not alter melphalan’s ability to promote cell death of Y79 cells.

Results: KZ-41 could inhibit melphalan-induced ICAM-1 levels and REC apoptosis. KZ-41 blocked increased ICAM-1 levels through p38MAPK activation and NF-κB inhibition; and decreased REC apoptosis likely through p38MAPK activation. KZ-41 did not alter melphalan’s effects on Y79 cells.

Conclusions: Use of KZ-41 to block NF-κB and activate P38MAPK protects REC against melphalan-induced upregulation of ICAM-1 and apoptosis.

Keywords: 503 drug toxicity/drug effects • 426 apoptosis/cell death • 557 inflammation  
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×