Lipid peroxidation dysregulation in ischemic stroke: plasma 4-HNE as a potential biomarker?
4-hydroxynonenal (4-HNE) is a major aldehyde produced during the lipid peroxidation of ω-6 polyunsaturated fatty acids. Recently, 4-HNE has been reported to contribute to the pathogenesis of neuronal diseases such as Alzheimer's disease. However, the role of 4-HNE in ischemic stroke is unclear yet. In this study, we found that plasma 4-HNE concentrations were higher in the genetic stroke-prone rats (stroke-prone spontaneously hypertensive rats) and experimental stroke rats with middle cerebral artery occlusion (MCAO). Moreover, administration of 4-HNE via intravenous injection before MCAO surgery not only enlarged cerebral ischemia-induced infarct area, but also increased oxidative stress in brain tissue, which was evidenced by the enhanced ROS/MPA levels, and the reduced GSH/GSSG ratio and MnSOD levels. Overexpression of aldehyde dehydrogenasesbcl-2 (ALDH2), an enzyme catalyses 4-HNE, rescued neuronal survival against 4-HNE treatment in PC12 cells. The plasma 4-HNE concentrations in patients with ischemic stroke were higher than those in control subjects. In a small sample population (N=60), the plasma 4-HNE concentration was positively correlated with the plasma homocysteine concentration, a risk factor for ischemic stroke. Taken together, our study suggests that the plasma 4-HNE level is a potential biomarker for ischemic stroke.
Department of Neurology, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
Wan-Chi
WC
Lee
Hau-Yang
HY
Wong
Yun-Yong
YY
Chai
Chan-Wei
CW
Shi
Naoya
N
Amino
Shizuki
S
Kikuchi
Shin-Hai
SH
Huang
D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000447:Aldehydes / Q000008:administration & dosage / Q000097:blood*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival; D006710:Homocysteine / Q000097:blood; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D016716:PC12 Cells; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000097:blood* / Q000473:pathology
D000447:Aldehydes; D015415:Biomarkers; D006710:Homocysteine; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C027576:4-hydroxy-2-nonenal