Bortezomib Effects on Human Microvascular Endothelium in vitro

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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

Fingerprint

Heme Oxygenase-1
Cyclooxygenase 2
Endothelium
Blood Vessels
NF-E2 Transcription Factor
Oxidative Stress
Endothelial Cells
Proteasome Inhibitors
Nuclear Proteins
Atherosclerosis
Cell Death
Antioxidants
Inflammation
Messenger RNA
Bortezomib
In Vitro Techniques

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Bortezomib Effects on Human Microvascular Endothelium in vitro. / Sahni, Abha; Thomasson, Erica D.; Shah, Riya; Sahni, Sanjeev.

In: Pharmacology, 27.08.2016, p. 272-278.

Research output: Contribution to journalArticle

@article{68bc6110af3544089b307b834942fcf7,
title = "Bortezomib Effects on Human Microvascular Endothelium in vitro",
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.",
keywords = "Bortezomib, Cyclooxygenase, Endothelium, Heme oxygenase, Nuclear factor erythroid 2-related factor 2",
author = "Abha Sahni and Thomasson, {Erica D.} and Riya Shah and Sanjeev Sahni",
year = "2016",
month = "8",
day = "27",
doi = "10.1159/000448757",
language = "English (US)",
pages = "272--278",
journal = "Pharmacology",
issn = "0031-7012",
publisher = "S. Karger AG",

}

TY - JOUR

T1 - Bortezomib Effects on Human Microvascular Endothelium in vitro

AU - Sahni, Abha

AU - Thomasson, Erica D.

AU - Shah, Riya

AU - Sahni, Sanjeev

PY - 2016/8/27

Y1 - 2016/8/27

N2 - 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.

AB - 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.

KW - Bortezomib

KW - Cyclooxygenase

KW - Endothelium

KW - Heme oxygenase

KW - Nuclear factor erythroid 2-related factor 2

UR - http://www.scopus.com/inward/record.url?scp=84991696924&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991696924&partnerID=8YFLogxK

U2 - 10.1159/000448757

DO - 10.1159/000448757

M3 - Article

C2 - 27578289

AN - SCOPUS:84991696924

SP - 272

EP - 278

JO - Pharmacology

JF - Pharmacology

SN - 0031-7012

ER -