Lipid peroxidation dysregulation in ischemic stroke: Plasma 4-HNE as a potential biomarker?

Lee, Wan-Chi; Wong, Hau-Yang; Chai, Yun-Yong; Shi, Chan-Wei; Amino, Naoya; Kikuchi, Shizuki; Huang, Shin-Hai

doi:10.1016/j.bbrc.2012.08.002

Cited by 97 publications

(82 citation statements)

References 43 publications

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“…Elevated levels of TG were associated with atherosclerosis, even in the absence of high cholesterol levels, which may be the reason why ALDH*2 allele was associated with cerebral infarction. But many other studies reported that ALDH2 protects against stroke by clearing 4-HNE (Yang et al 2014;Guo et al 2013;Lee et al 2012). Our research revealed that the ALDH2*2 allele is associated with cerebral infarction, this is consistent with the most previous studies, but further studies are needed to uncover the precise mechanism behind the regulation of ALDH2 in cerebral infarction.…”

Section: Discussionsupporting

confidence: 91%

“…Another research in Korean also showed that carrying the wild-type allele of the ALDH2 polymorphism increased stroke risk among men (Shin et al 2015). On the contrary, the majority recent studies found that ALDH2 can protect against stroke by clearing 4-HNE (Guo et al 2013;Sun and Ren 2013;Lai et al 2012;Lee et al 2012). Therefore, it is necessary to conduct a research involving a large sample to evaluate the association between ALDH2 polymorphism and cerebral infarction.…”

Section: Introductionmentioning

confidence: 99%

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ALDH2*2 Allele is a Negative Risk Factor for Cerebral Infarction in Chinese Women

Zhao

et al. 2015

Biochem Genet

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Unlike its reported role in the cardiovascular diseases, little information is available for mitochondrial aldehyde dehydrogenase 2 (ALDH2) in the cerebrovascular function. We investigated the different effects of ALDH2 genotypes on the risk of cerebral infarction between the genders, because different genders had different smoking and/or dinking status which are also risk factors for cerebral infarction. 247 healthy Chinese Han people (controls, group 1), 287 Chinese Han male patients with cerebral infarction (group 2), and 82 Chinese Han female patients with cerebral infarction (group 3) were involved in this study. The frequencies of the ALDH2*2 allele in group 3 were significantly higher than those in other groups (with P = 0.001 and P = 0.002, respectively). The difference of ALDH2*2 allele frequency between group 1 and group 2 was not significant (P = 0.652). After adjustment for smoking and drinking status, the male patients without smoking or drinking status (group 4) had higher ALDH2*2 allele frequency than group 1, but the difference was still not significant (P = 0.139). Thus, we conclude that ALDH2*2 allele may be a significant negative risk factor for cerebral infarction in Chinese women [odds ratio (OR) = 2.207, 95% CI 1.416-3.439]. But for Chinese male patients, the negative effects of ALDH2*2 allele on cerebral infarction which might be concealed by other risk factors were not significant.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

ALDH2*2 Allele is a Negative Risk Factor for Cerebral Infarction in Chinese Women

Zhao

et al. 2015

Biochem Genet

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“…[15][16][17] Since HNE readily forms adducts with proteins, measurement of unreacted HNE represents a lower estimate of levels produced in vivo. In this study we selected concentrations that could be generated locally at a site of oxidative stress and mediate acute stress to neurons in regions subject to neurodegeneration, stroke or seizure.…”

Section: Basic Research Papermentioning

confidence: 99%

Inhibition of glycolysis attenuates 4-hydroxynonenal-dependent autophagy and exacerbates apoptosis in differentiated SH-SY5Y neuroblastoma cells

et al. 2013

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“…The physiological concentrations of 4-HNE in interstitial fluids range from 0.3 to 5 μM and increase by 10–100 fold under pathological conditions [12], [13]. Although 4-HNE concentrations are lower in plasma than in tissues, elevated plasma 4-HNE concentrations (1–10 μM) have been observed in patients experiencing ischemic brain hemorrhage and stroke [14], [15].…”

Section: Introductionmentioning

confidence: 99%

“…Considering that the relatively lower concentration (ca. 10 μM) of 4-HNE can be maintained in plasma for a prolonged period in the brain hemorrhage and stroke [14], [15], it is requested to examine the effects of both short- and long-term effects on the cardiac ion channels.…”

Section: Introductionmentioning

confidence: 99%

Suppression of hERG K+ current and cardiac action potential prolongation by 4-hydroxynonenal via dual mechanisms

Choi

Jeon

et al. 2018

Redox Biology

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Oxidative stress under pathological conditions, such as ischemia/reperfusion and inflammation, results in the production of various reactive chemicals. Of these chemicals, 4-hydroxynonenal (4-HNE), a peroxidation product of ω6-polyunsaturated fatty acid, has garnered significant attention. However, the effect of 4-HNE on cardiac electrophysiology has not yet been reported. In the present study, we investigated the effects of 4-HNE on several cardiac ion channels, including human ether-a-go-go-related (hERG) channels, using the whole-cell patch clamp technique. Short-term exposure to 100 μM 4-HNE (4-HNE100S), which mimics local levels under oxidative stress, decreased the amplitudes of rapidly activating delayed rectifier K+ current (IKr) in guinea pig ventricular myocytes (GPVMs) and HEK293T cells overexpressing hERG (IhERG). MS analysis revealed the formation of 4-HNE-hERG adduct on specific amino acid residues, including C276, K595, H70, and H687. Long-term treatment (1–3 h) with 10 μM 4-HNE (4-HNE10L), suppressed IKr and IhERG, but not IKs and ICa,L. Action potential duration (APD) of GPVMs was prolonged by 37% and 64% by 4-HNE100S and 4-HNE10L, respectively. Western blot analysis using surface biotinylation revealed a reduction in mature membrane hERG protein after treatment with 4-HNE10L. Proteasomal degradation inhibitors, such as bortezomib, prevented the 4-HNE10L-induced decrease in mature hERG, suggesting a retrograde degradation of membrane hERG due to 4-HNE. Taken together, 4-HNE100S and 4-HNE10L suppressed IhERG via functional inhibition and downregulation of membrane expression of hERG, respectively. The exposure of 4-HNE under pathological oxidative stress may increase the risk of proarrhythmic events via APD prolongation.

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Lipid peroxidation dysregulation in ischemic stroke: Plasma 4-HNE as a potential biomarker?

Cited by 97 publications

References 43 publications

ALDH2*2 Allele is a Negative Risk Factor for Cerebral Infarction in Chinese Women

ALDH2*2 Allele is a Negative Risk Factor for Cerebral Infarction in Chinese Women

Inhibition of glycolysis attenuates 4-hydroxynonenal-dependent autophagy and exacerbates apoptosis in differentiated SH-SY5Y neuroblastoma cells

Suppression of hERG K+ current and cardiac action potential prolongation by 4-hydroxynonenal via dual mechanisms

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