4-Hydroxynonenal as a second messenger of free radicals and growth modifying factor

Žarković, Neven; Žarković, Kamelija; Schaur, R. J.; Štolc, Svorad; Schlag, G.; Redl, Heinz; Waeg, Georg; Borović, Suzana; Lončarić, Iva; Jurić, Gordana; Hlavka, V

doi:10.1016/s0024-3205(99)00444-0

Cited by 70 publications

(48 citation statements)

References 6 publications

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“…To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars adhesion, adherens, and TJ proteins as well as integrin. These findings, along with HNE abundance in the BBB found under various pathophysiological circumstances (277,356) and as shown in Figure 15, suggest that HNE is associated with several regulatory functions, including post-traumatic recovery (355,359).…”

Section: Activated Microglia and Bbb Impairmentmentioning

confidence: 77%

Redox Control of Microglial Function: Molecular Mechanisms and Functional Significance

Rojo

McBean²,

Cindrić³

et al. 2014

Antioxidants & Redox Signaling

262

242

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Neurodegenerative diseases are characterized by chronic microglial over-activation and oxidative stress. It is now beginning to be recognized that reactive oxygen species (ROS) produced by either microglia or the surrounding environment not only impact neurons but also modulate microglial activity. In this review, we first analyze the hallmarks of pro-inflammatory and anti-inflammatory phenotypes of microglia and their regulation by ROS. Then, we consider the production of reactive oxygen and nitrogen species by NADPH oxidases and nitric oxide synthases and the new findings that also indicate an essential role of glutathione (c-glutamyl-lcysteinylglycine) in redox homeostasis of microglia. The effect of oxidant modification of macromolecules on signaling is analyzed at the level of oxidized lipid by-products and sulfhydryl modification of microglial proteins. Redox signaling has a profound impact on two transcription factors that modulate microglial fate, nuclear factor kappa-light-chain-enhancer of activated B cells, and nuclear factor (erythroid-derived 2)-like 2, master regulators of the pro-inflammatory and antioxidant responses of microglia, respectively. The relevance of these proteins in the modulation of microglial activity and the interplay between them will be evaluated. Finally, the relevance of ROS in altering blood brain barrier permeability is discussed. Recent examples of the importance of these findings in the onset or progression of neurodegenerative diseases are also discussed. This review should provide a profound insight into the role of redox homeostasis in microglial activity and help in the identification of new promising targets to control neuroinflammation through redox control of the brain.

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Section: Activated Microglia and Bbb Impairmentmentioning

confidence: 77%

Redox Control of Microglial Function: Molecular Mechanisms and Functional Significance

Rojo

McBean²,

Cindrić³

et al. 2014

Antioxidants & Redox Signaling

262

242

View full text Add to dashboard Cite

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“…4-Hydroxynonenal is considered as a reliable biomarker of lipid peroxidation, and it is also a cytotoxic and a genotoxic agent, a real ''second messenger of oxidative stress,'' via alteration(s) of cellular functions and the formation of exocyclic DNA adducts (14). 4-Hydroxynonenal is also considered as a cell signaling molecule (15). However, 4-hydroxynonenal is not excreted into urine and thus cannot be directly measured from noninvasive sampling techniques, although DHN-MA, the major urinary metabolite of 4-hydroxynonenal, bears the same advantages without this drawback.…”

Section: Cancer Epidemiology Biomarkers and Prevention 2277mentioning

confidence: 99%

New Marker of Colon Cancer Risk Associated with Heme Intake: 1,4-Dihydroxynonane Mercapturic Acid

Pierre

Peiro

Taché

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Red meat consumption is associated with an increased risk of colon cancer. Animal studies show that heme, found in red meat, promotes preneoplastic lesions in the colon, probably due to the oxidative properties of this compound. End products of lipid peroxidation, such as 4-hydroxynonenal metabolites or 8-iso-prostaglandin-F 2 A (8-iso-PGF 2 A), could reflect this oxidative process and could be used as biomarkers of colon cancer risk associated with heme intake. Methods: We measured urinary excretion of 8-iso-PGF 2 A and 1,4-dihydroxynonane mercapturic acid (DHN-MA), the major urinary metabolite of 4-hydroxynonenal, in three studies. In a short-term and a carcinogenesis long-term animal study, we fed rats four different diets (control, chicken, beef, and blood sausage as a high heme diet). In a randomized crossover human study, four different diets were fed (a 60 g/d red meat

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“…HNE affects mitochondrial respiratory functions. Signaling functions of HNE were also described [10][11][12][13][14] . HNE reacts with lysine, histidine, and cysteine residues.…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress in Renal Anemia of Hemodialysis Patients Is Mitigated by Epoetin Treatment

Siems

Carluccio²,

Radenkovic

et al. 2005

Kidney Blood Press Res

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Background/Aims: Oxidative stress often occurs in chronic hemodialysis (HD) patients. The objective of our study was to investigate the interrelationship between oxidative stress and the degree of renal anemia. Methods: In 107 consecutive HD patients, serum concentrations of two major aldehydic lipid peroxidation (LPO) products, 4-hydroxynonenal (HNE) and malondialdehyde (MDA), and of protein carbonyls were analyzed as parameters of oxidative stress and related to the degree of renal anemia. Additionally, in 76 patients treated with epoetin long-term changes in the serum levels of aldehydic LPO products were observed. Results: In HD patients, serum levels of HNE, MDA, and protein carbonyls are increased in comparison to controls. The lower the hemoglobin, i.e. the stronger the degree of renal anemia, the higher the serum concentrations of HNE, MDA, and protein carbonyls. The HNE and MDA levels decreased during HD. Long-term studies on the correction of renal anemia by epoetin demonstrated a mitigation of oxidative stress during this therapy. During periods of 1 and 2 years, it was observed that the serum levels of HNE and MDA could be reduced. Conclusion: Chronic renal failure is connected with oxidative stress which correlates with the degree of renal anemia, and the serum levels of aldehydic LPO products could be reduced during correction of renal anemia by epoetin.

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4-Hydroxynonenal as a second messenger of free radicals and growth modifying factor

Cited by 70 publications

References 6 publications

Redox Control of Microglial Function: Molecular Mechanisms and Functional Significance

Redox Control of Microglial Function: Molecular Mechanisms and Functional Significance

New Marker of Colon Cancer Risk Associated with Heme Intake: 1,4-Dihydroxynonane Mercapturic Acid

Oxidative Stress in Renal Anemia of Hemodialysis Patients Is Mitigated by Epoetin Treatment

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