Bortezomib Effects on Human Microvascular Endothelium in vitro

Abha Sahni, Erica D. Thomasson, Riya Shah, Sanjeev Sahni

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Cellular oxidative stress in the endothelium of blood vessels leads to several pathophysiological sequelae, including vascular damage and dysfunction, inflammation and atherosclerosis. Heme oxygenase-1 (HO-1) provides protection against oxidative stress-induced cell death and plays a crucial role in the regulation of cyclooxygenase-2 (COX-2) in endothelial cells. In the present study, we have investigated the effects of bortezomib, a clinically used proteasome inhibitor, on the regulation of HO-1 and COX-2 in cultured human microvascular endothelial cells (HMECs). Bortezomib treatment of HMECS induced dose- and time-dependent expression of HO-1 and COX-2 mRNA and protein, and triggered nuclear translocation of nuclear factor erythroid 2-related transcription factor (Nrf2). These findings suggest that HO-1/COX-2-mediated induction of antioxidant mechanisms via Nrf2 activation may contribute to the cytoprotective effects of bortezomib in microvascular endothelium.

Original languageEnglish (US)
Pages (from-to)272-278
Number of pages7
JournalPharmacology
DOIs
StateAccepted/In press - Aug 27 2016

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Keywords

  • Bortezomib
  • Cyclooxygenase
  • Endothelium
  • Heme oxygenase
  • Nuclear factor erythroid 2-related factor 2

ASJC Scopus subject areas

  • Pharmacology

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