PMID- 23836589
OWN - NLM
STAT- MEDLINE
DCOM- 20140617
LR  - 20211203
IS  - 1613-4133 (Electronic)
IS  - 1613-4125 (Linking)
VI  - 57
IP  - 11
DP  - 2013 Nov
TI  - Isothiocyanates protect against oxidized LDL-induced endothelial dysfunction by 
      upregulating Nrf2-dependent antioxidation and suppressing NFkappaB activation.
PG  - 1918-30
LID - 10.1002/mnfr.201300063 [doi]
AB  - SCOPE: Oxidative stress plays a pivotal role in the pathophysiology of 
      cardiovascular diseases. Oxidized low-density lipoprotein (oxLDL) is a key 
      contributor to atherogenesis through multiple mechanisms. In this study, we 
      investigated the protection by three structurally related isothiocyanates, i.e., 
      sulforaphane (SFN), benzyl isothiocyanate (BITC), and phenethyl isocyanate 
      (PEITC), against oxLDL-induced leukocyte adhesion to vascular endothelium and the 
      mechanism involved. METHODS AND RESULTS: The protection against oxLDL-induced 
      endothelial dysfunction by isothiocyanates was studied in human umbilical vein 
      endothelial cells (HUVECs). oxLDL increased reactive oxygen species (ROS) 
      production, stimulated nuclear factor-kappaB (NFkappaB) activation, and enhanced 
      intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 
      (VCAM-1), and E-selectin expression in HUVECs, which led to promotion of monocyte 
      adhesion to HUVECs. Treatment with SFN, BITC, and PEITC (0-10 muM) 
      dose-dependently induced heme oxygenase (HO)-1, glutamate cysteine ligase (GCL) 
      catalytic and modifier subunit expression, intracellular glutathione content, and 
      antioxidant response element (ARE)-luciferase reporter activity. SFN, BITC, and 
      PEITC pretreatment reversed oxLDL-induced ROS production, NFkappaB nuclear 
      translocation, kappaB-reporter activity, ICAM-1, VCAM-1, and E-selectin expression, 
      and monocyte adhesion to endothelial cells. Both heme oxygenase 1 (HO-1) and 
      nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown attenuated the 
      isothiocyanate inhibition of oxLDL-induced ROS production, kappaB-reporter activity, 
      and adhesion molecule expression. CONCLUSION: SFN, BITC, and PEITC protect 
      against oxLDL-induced endothelial damage by upregulating Nrf2-dependent HO-1 and 
      GCL expression, which leads to inhibition of NFkappaB activation and ICAM-1, VCAM-1, 
      and E-selectin expression.
CI  - (c) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Huang, Chin-Shiu
AU  - Huang CS
AD  - Department of Health and Nutrition Biotechnology, Asia University, Taichung, 
      Taiwan.
FAU - Lin, Ai-Hsuan
AU  - Lin AH
FAU - Liu, Cheng-Tzu
AU  - Liu CT
FAU - Tsai, Chia-Wen
AU  - Tsai CW
FAU - Chang, Ing-Shr
AU  - Chang IS
FAU - Chen, Haw-Wen
AU  - Chen HW
FAU - Lii, Chong-Kuei
AU  - Lii CK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130709
PL  - Germany
TA  - Mol Nutr Food Res
JT  - Molecular nutrition & food research
JID - 101231818
RN  - 0 (Antioxidants)
RN  - 0 (E-Selectin)
RN  - 0 (ICAM1 protein, human)
RN  - 0 (Isothiocyanates)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (SELE protein, human)
RN  - 0 (Sulfoxides)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 0 (oxidized low density lipoprotein)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 871J6YOR8Q (benzyl isothiocyanate)
RN  - EC 1.14.14.18 (HMOX1 protein, human)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 6.3.2.2 (Glutamate-Cysteine Ligase)
RN  - GA49J4310U (sulforaphane)
SB  - IM
MH  - Antioxidant Response Elements/drug effects
MH  - Antioxidants/pharmacology
MH  - Cell Adhesion/drug effects
MH  - Dose-Response Relationship, Drug
MH  - E-Selectin/genetics/metabolism
MH  - Glutamate-Cysteine Ligase/genetics/metabolism
MH  - Heme Oxygenase-1/genetics/metabolism
MH  - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/genetics/metabolism
MH  - Isothiocyanates/*pharmacology
MH  - Leukocytes/drug effects/metabolism
MH  - Lipoproteins, LDL/*adverse effects
MH  - NF-E2-Related Factor 2/*genetics/metabolism
MH  - NF-kappa B/antagonists & inhibitors/genetics/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Sulfoxides
MH  - *Up-Regulation
MH  - Vascular Cell Adhesion Molecule-1/genetics/metabolism
OTO - NOTNLM
OT  - Adhesion molecules
OT  - Glutamate cysteine ligase
OT  - Heme oxygenase 1
OT  - Isothiocyanates
OT  - Nuclear factor erythroid 2-related factor 2 (Nrf2)
OT  - Nuclear factor-kappaB (NFkappaB)
OT  - Oxidized LDL
EDAT- 2013/07/10 06:00
MHDA- 2014/06/18 06:00
CRDT- 2013/07/10 06:00
PHST- 2013/01/21 00:00 [received]
PHST- 2013/04/16 00:00 [revised]
PHST- 2013/04/21 00:00 [accepted]
PHST- 2013/07/10 06:00 [entrez]
PHST- 2013/07/10 06:00 [pubmed]
PHST- 2014/06/18 06:00 [medline]
AID - 10.1002/mnfr.201300063 [doi]
PST - ppublish
SO  - Mol Nutr Food Res. 2013 Nov;57(11):1918-30. doi: 10.1002/mnfr.201300063. Epub 
      2013 Jul 9.