Covalent Modification of Amino Acid Nucleophiles by the Lipid Peroxidation Products 4-Hydroxy-2-nonenal and 4-Oxo-2-nonenal

Doorn, Jonathan A.; Petersen, Dennis R.

doi:10.1021/tx025590o

Cited by 289 publications

(349 citation statements)

References 33 publications

Supporting

Mentioning

328

Contrasting

Order By: Relevance

“…Various reactive oxygen species react with all cellular components; the hydroxyl radical-mediated peroxidation of polyunsaturated acyl chains of glycerophospholipids is particularly harmful because it results in the formation of lipid peroxidation production considered second messengers and the ultimate mediator of toxic effects elicited by oxidative stress. Of the lipid peroxidation products, 4-HNE is the most abundant and reactive aldehydic product derived from the peroxidation of n-6 polyunsaturated fatty acids (22)(23)(24). The results from our study are consistent with previous clinical observations and experimental investigations showing that obesity is associated with decreased plasma adiponectin concentrations and increased production of lipid peroxidation products in adipose tissue, including 4-HNE (13,14).…”

Section: Discussionsupporting

confidence: 89%

Association of 4-hydroxynonenal with classical adipokines and insulin resistance in a Chinese non-diabetic obese population

Guo¹,

Zhang²,

Zhang³

et al. 2017

Nutr Hosp

View full text Add to dashboard Cite

Background: The prevalence of obesity is increasing worldwide. Oxidative stress plays an etiological role in a variety of obesity-related metabolic disorders. 4-hydroxynonenal (4-HNE) is the most abundant and reactive aldehydic product derived from the peroxidation of n-6 polyunsaturated fatty acids with diverse biological effects that are not well detailed. Obesity is associated with decreased plasma adiponectin concentrations and increased production of lipid peroxidation products, including 4-HNE, in adipose tissue. There may be some association between the level of adipokines and 4-HNE. Material and methods:To analyze the associations between 4-HNE and classical adipokines, namely, adiponectin and leptin in a Chinese population, the plasma 4-HNE, adiponectin and leptin levels of 160 non-diabetic obese (NDO) patients and 160 healthy subjects were determined by ELISA, and their associations with adiposity, glucose, lipid profi les, insulin secretion and insulin sensitivity were studied. Results: Plasma 4-HNE levels were signifi cantly increased in patients with NDO compared with healthy controls (p < 0.01). 4-HNE was negatively correlated with adiponectin and positively correlated with leptin. The plasma levels of 4-HNE were signifi cantly correlated to several parameters involved in body mass index (BMI) and insulin resistance (IR). The 4-HNE levels were positively correlated with BMI and negatively correlated with insulin sensitivity. Conclusion: We conclude that 4-HNE is associated with the secretion of adiponectin and leptin and is correlated with IR in NDO humans. These fi ndings indicate a pro-infl ammatory role of 4-HNE in NDO patients, which supports the potential role of 4-HNE in the development of obesity-related disorders.

show abstract

Section: Discussionsupporting

confidence: 89%

Association of 4-hydroxynonenal with classical adipokines and insulin resistance in a Chinese non-diabetic obese population

Guo¹,

Zhang²,

Zhang³

et al. 2017

Nutr Hosp

View full text Add to dashboard Cite

show abstract

“…4-HNE is an electrophile that reacts with amino acid side chains of proteins (11,16,54), thereby altering protein function (2, 20, 45, 56). 4-HNE, an end product of lipid peroxidation, is widely recognized as a specific marker of oxidative stress (41); increased reactive oxygen species (ROS) levels are an important trigger for insulin resistance in numerous settings (25).…”

Section: Discussionmentioning

confidence: 99%

Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat

Morris¹,

Laye²,

Lees³

et al. 2008

Journal of Applied Physiology

View full text Add to dashboard Cite

Morris RT, Laye MJ, Lees SJ, Rector RS, Thyfault JP, Booth FW. Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat. J Appl Physiol 104: 708-715, 2008. First published December 13, 2007 doi:10.1152/japplphysiol.01034.2007.-The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a model of hyperphagic obesity in which the animals retain the desire to run voluntarily. Running wheels were provided for 4-wk-old OLETF rats for 16 wk before they were killed 5 h (WL5), 53 h (WL53), or 173 h (WL173) after the wheels were locked. Sedentary (SED) OLETF rats that were not given access to running wheels served as age-matched cohorts. Epididymal fat pad mass, adipocyte volume, and adipocyte number were 58%, 39%, and 47% less, respectively, in WL5 than SED rats. Contrary to cessation of daily running in Fischer 344 ϫ Brown Norway rats, epididymal fat did not increase during the first 173 h of running cessation in the OLETF runners. Serum insulin and glucose levels were 77% and 29% less, respectively, in WL5 than SED rats. Oil red O staining for intramyocellular lipid accumulation was not statistically different among groups. However, lipid peroxidation levels, as determined by total trans-4-hydroxy-2-nonenal (4-HNE) and 4-HNE normalized to oil red O, was higher in epitrochlearis muscles of SED than WL5, WL53, and WL173 rats. mRNA levels of glutathione S-transferase-␣ type 4, an enzyme involved in cellular defense against electrophilic compounds such as 4-HNE, were higher in epitrochlearis muscle of WL53 than WL173 and SED rats. In contrast, 4-HNE levels in omental fat were unaltered. Epitrochlearis muscle palmitate oxidation and relative transcript levels for peroxisome proliferator-activated receptor-␦ and peroxisome proliferator-activated receptor-␥ coactivator type 1 were surprisingly not different between runners and SED rats. In summary, voluntary running was associated with lower levels of lipid peroxidation in skeletal muscle without significant changes in intramyocellular lipids or mitochondrial markers in OLETF rats at 20 wk of age. Therefore, even in a genetic animal model of extreme overeating, daily physical activity promotes improved health of skeletal muscle. physical activity; oxidative stress; chronic disease THE INCIDENCE OF OVERWEIGHT in children and adolescents has tripled to 17.1% in 2004 from the late 1960s in the United States (40). Obesity is caused by a positive energy balance, with excess energy intake and insufficient physical activity being major causal factors. An understanding of the biological basis for energy partitioning from fat to skeletal muscle is imperative for prevention of fat gain as young subjects grow to adults.The Otsuka Long-Evans Tokushima fatty (OLETF) rat, which was selectively bred for null expression of the cholecystokinin (CCK)-1 receptor (27), is an animal model characterized by hyperphagia, obesity, decreased glucose infusion rate in a euglycemic clamp at 16 wk of age, and hyperinsulinemia at 24 wk of age in respons...

show abstract

“…Most of these have focused on HNE, and more recently ONE, as the major products that react with proteins (11)(12)(13)(14). However, the most important electrophile involved in protein modification is unknown.…”

Section: Discussionmentioning

confidence: 99%

Covalent Adducts Arising from the Decomposition Products of Lipid Hydroperoxides in the Presence of Cytochrome c

Williams

Wishnok

Tannenbaum

2007

Chem. Res. Toxicol.

View full text Add to dashboard Cite

Polyunsaturated fatty acids can be converted to lipid hydroperoxides through non-enzymatic and enzymatic pathways. The prototypic ω-6 lipid hydroperoxide 13-hydroperoxy-octadecadienoic acid (13-HPODE) decomposes homolytically to form highly reactiveα,β-unsaturated aldehydes, such as 9,12-dioxo-10(E)-dodecenoic acid (DODE), 4-oxo-2(E)-nonenal (ONE), 4,5-epoxy-2(E)-decenal (EDE), and 4-hydroxy-2(E)-nonenal (HNE), that can form covalent adducts with DNA. Both 4-oxo-2 (E)-nonenal and 4-hydroxy-2(E)-nonenal can also modify proteins to form products that can potentially serve as biomarkers of lipid hydroperoxide-mediated macromolecule damage. In this study cytochrome C was used to identify and characterize the modification sites individually for each of these aldehydes and also to determine the most abundant adduct formed following decomposition of 13-HPODE. The adducts were characterized by ESI-TOF/MS analysis of the intact proteins and by a combination of ESI-ion-trap/MS n and quadrupole-TOF/MS/MS analysis of the tryptic and chymotryptic peptides.

show abstract

Covalent Modification of Amino Acid Nucleophiles by the Lipid Peroxidation Products 4-Hydroxy-2-nonenal and 4-Oxo-2-nonenal

Cited by 289 publications

References 33 publications

Association of 4-hydroxynonenal with classical adipokines and insulin resistance in a Chinese non-diabetic obese population

Association of 4-hydroxynonenal with classical adipokines and insulin resistance in a Chinese non-diabetic obese population

Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat

Covalent Adducts Arising from the Decomposition Products of Lipid Hydroperoxides in the Presence of Cytochrome c

Contact Info

Product

Resources

About