Lysophosphatidylcholine enhances oxidative stress via the 5-lipoxygenase pathway in rat aorta during aging.
Lysophosphatidylcholine (LPC) is a lysolipid, acting as a potent cellular mediator of various biological processes. The purpose of this study was to define the role of LPC as a possible causative factor of disrupted redox balance in aged aorta from rats. In this study, we found elevated serum LPC levels in 24-month-old rats that were correlated with the age-related increase in cytosolic phospholipase A(2) (PLA(2)) activity. We also found that aortas from old rats showed increased 5-lipoxygenase (5-LO) activity. With the LPC-treated endothelial cells (YPEN-1 cells), we observed a rapid generation of reactive species, leading to enhanced oxidative stress. Our further investigations using specific 5-LO inhibitors led to the identification of a 5-LO pathway as the reactive species production source in the LPC-treated cells. Additional validation of this 5-LO pathway was made by the detection of increased leukotriene B4 generation in the LPC-treated cells. These in vitro data supported findings of increased expression and activation of aortic 5-LO in old rats by LPC. Together, our data strongly suggested that LPC caused the enhancement of oxidative stress in aged aorta through reactive species generation by an activated 5-LO pathway. LPC may well be an important contributor to age-related oxidative stress in aging aorta.
Zou
Yani
Y
College of Pharmacy, Aging Tissue Bank, Busan, South Korea.
Kim
Dae Hyun
DH
Jung
Kyung Jin
KJ
Heo
Hyoung-Sam
HS
Kim
Chul Hong
CH
Baik
Hyung Suk
HS
Yu
Byung Pal
BP
Yokozawa
Takako
T
Chung
Hae Young
HY
D000375:Aging / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D054513:Group IV Phospholipases A2 / Q000378:metabolism / Q000502:physiology; D008244:Lysophosphatidylcholines / Q000097:blood / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013047:Specific Pathogen-Free Organisms
D008244:Lysophosphatidylcholines; D017382:Reactive Oxygen Species; D001094:Arachidonate 5-Lipoxygenase; D054513:Group IV Phospholipases A2