Essential role of NOXA1 in generation of reactive oxygen species induced by oxidized low-density lipoprotein in human vascular endothelial cells.
Oxidative stress induced by superoxide plays an important role in pathogenesis of cardiovascular diseases. NAD(P)H oxidase is a principal enzymatic origin for superoxide in vasculature. Recently, novel homologues of cytosolic components of NAD(P)H oxidase, Nox organizer 1 (NOXO1) and Nox activator 1 (NOXA1), are identified. On the other hand, oxidized low-density lipoprotein (ox-LDL) generates reactive oxygen species (ROS) in endothelial cells via lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). In the present investigation, the authors examined the expression, the regulation, and the role of NOXA1 in the generation of ROS in endothelial cells. The expression of NOXA1 was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). Dihydroethidium method showed that ox-LDL and angiotensin II increased the generation of intracellular ROS. Once the expression of p22(phox) or NOXA1 was suppressed by siRNA, the generation of ROS induced by ox-LDL and angiotensin II were potently decreased. Moreover, the expression of NOXA1 was increased by ox-LDL in a time-and dose-dependent manner. In conclusion, endothelial NOXA1 plays an essential role in generation of ROS. Ox-LDL not only increased the generation of ROS via LOX-1, but also enhanced the expression of NOXA1 in endothelial cells. NOXA1 is likely a key player that links ox-LDL with the activation of endothelial NAD(P)H oxidase.
Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Tomoyuki
T
Honjo
Kazunori
K
Otsui
Rio
R
Shiraki
Seinosuke
S
Kawashima
Tatsuya
T
Sawamura
Mitsuhiro
M
Yokoyama
Nobutaka
N
Inoue
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D008077:Lipoproteins, LDL; C476420:NOXA1 protein, human; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein