4-Hydroxynonenal – major bioactive marker of lipid peroxidation

While oxidative stress is generally considered mostly as pathogenic component of stress and age associated diseases, reactive aldehydes such as 4-hydroxy-2-nonenal (HNE) are considered mostly as the end-products of lipid peroxidation, which act as a “second toxic messenger of free radicals”. However, findings of growth regulating activities of HNE that overlapped with the development of the first monoclonal and polyclonal antibodies specific for the HNE-protein adducts led to the introduction of qualitative and quantitative determinations of the HNE presence in various (patho)physiological processes and to the change of consideration of the aldehyde’s bioactivities from toxicity into cell signaling, growth regulation and hormesis.Thus, the progress in the fields of the redox signaling and broad bioactivities or reactive oxygen and nitrogen species changed our overall approach to oxidative stress and to consideration of HNE not only as toxic but more general as a “second messenger of free radicals” and the growth regulating factor. Moreover, findings of the HNE-protein adducts in various organs under physiological circumstances support the concept of “oxidative homeostasis”, which implies that oxidative stress and lipid peroxidation are not only pathological but also physiological processes. Accordingly, HNE could play important role in oxidative homeostasis, while complementary research approaches might reveal the relevance of the aldehydic-protein adducts as major bioactive markers of oxidative stress, lipid peroxidation and oxidative homeostasis.Keywords 4-Hydroxynonenal, lipid peroxidation, oxidative stress, pathophysiology, reactive aldehydes aling, growth regulation and hormesis.  

Low back pain as the presenting sign in a patient with primary extradural melanoma of the thoracic spine - A metastatic disease 17 Years after complete surgical resection

Primary spinal melanomas are extremely rare lesions. In 1906, Hirschberg reported the first primary spinal melanoma, and since then only 40 new cases have been reported. A 47-year-old man was admitted suffering from low back pain, fatigue and loss of body weight persisting for three months. He had a 17-year-old history of an operated primary spinal melanoma from T7-T9, which had remained stable for these 17 years. Routine laboratory findings and clinical symptoms aroused suspicion of a metastatic disease. Multislice computed tomography and magnetic resonance imaging revealed stage-IV melanoma with thoracic, abdominal and skeletal metastases without the recurrence of the primary process. Transiliac crest core bone biopsy confirmed the diagnosis of metastatic melanoma. It is important to know that in all cases of back ore skeletal pain and unexplained weight loss, malignancy must always be considered in the differential diagnosis, especially in the subjects with a positive medical history. Patients who have back, skeletal, or joint pain that is unresponsive to a few weeks of conservative treatment or have known risk factors with or without serious etiology, are candidates for imaging studies. The present case demonstrates that complete surgical resection alone may result in a favourable outcome, but regular medical follow-up for an extended period, with the purpose of an early detection of a metastatic disease, is highly recommended

The 4-Hydroxynonenal–Protein Adducts and Their Biological Relevance: Are Some Proteins Preferred Targets?

It is well known that oxidative stress and lipid peroxidation (LPO) play a role in physiology and pathology. The most studied LPO product with pleiotropic capabilities is 4-hydroxynonenal (4-HNE). It is considered as an important mediator of cellular signaling processes and a second messenger of reactive oxygen species. The effects of 4-HNE are mainly attributed to its adduction with proteins. Whereas the Michael adducts thus formed are preferred in an order of potency of cysteine > histidine > lysine over Schiff base formation, it is not known which proteins are the preferred targets for 4-HNE under what physiological or pathological conditions. In this review, we briefly discuss the methods used to identify 4-HNE–protein adducts, the progress of mass spectrometry in deciphering the specific protein targets, and their biological relevance, focusing on the role of 4-HNE protein adducts in the adaptive response through modulation of the NRF2/KEAP1 pathway and ferroptosis

Interval hypoxic training in complex treatment of Helicobacter pylori-associated peptic ulcer disease

This study was aimed to demonstrate the efficacy of interval hypoxic training (IHT) in complex treatment of Helicobacter pylori-associated duodenal peptic ulcer disease (DPUD) by parameters of aerobic metabolism and indexes of heart rate variability (HRV). Eighty patients with H. pylori-associated DPUD were included into the study, mean age 32±1.8 yrs, duration of the disease up to 10 years (66.3 %). IHT was modulated using Frolov's hypoxicator (TDI-01) for 30 days after standard eradication therapy. Daily hypoxic sessions consisted of three one-minute sessions, one two-minute, and one three-minute sessions separated by one-minute intervals of room-air breathing. Use of IHT resulted in more efficient elimination of clinical symptoms, histological hallmarks of inflammation and signs of oxidative stress in glandulocytes of the gastric mucosa as determined by 4-hydroxynonenal accumulation. Moderate prooxidant activity of IHT was demonstrated by the increased level of TBARS and oxidatively modified products, normalization of hydroperoxides, middle mass molecules and atherogenic beta-lipoproteins with simultaneous increase in catalase activity and mild decline of SOD activity. Therefore, IHT appeared to be accompanied by higher intensity of redox reactions and enhanced regeneratory processes in cells and tissues. Significant increase in HRV was also noted. Such changes were associated with reduction of inflammation signs and modulation of the autonomic homeostasis in DPUD patients. In general, use of IHT in complex treatment of H. pylori in DPUD patients can be recommended to increase resistance to oxidative stress and to modulate autonomic balance and oxidative homeostasis

HNE-protein adducts formation in different pre-carcinogenic stages of hepatitis in LEC rats

International audienceLipid peroxidation is highly associated with chronic degenerative diseases such as cancer. 4-hydroxy-2-nonenal is one of the major products of lipid peroxidation. 4-hydroxy-2-nonenal can interact with biomolecules, changing their conformation and activity. This study presents 4-hydroxy-2-nonenal-protein adducts formation in the first stages of Long-Evans Cinnamon rat hepatitis, a well recognized model for oxidative stress-associated hepatocarcinogenesis. 4-hydroxy-2-nonenal-protein adducts appeared in hepatocyte cytoplasm before the beginning of hepatitis and their presence was very strong during hepatitis, while a transient perinuclear expression of 4-hydroxy-2-nonenal-protein adducts was shown mainly at early hepatitis stages. 4-hydroxy-2-nonenal-protein adducts formation correlated to the expression of the tumour marker glutathione S-transferase P-form. These results show that lipid peroxidation modification of proteins might be implicated in the first stages of hepatocyte cancer initiation in Long-Evans Cinnamon rats

Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer

An oxidative degradation product of the polyunsaturated fatty acids, 4-hydroxynonenal (4-HNE), is of particular interest in cancer research due to its concentration-dependent pleiotropic activities affecting cellular antioxidants, metabolism, and growth control. Although an increase in oxidative stress and lipid peroxidation was already associated with prostate cancer progression a few decades ago, the knowledge of the involvement of 4-HNE in prostate cancer tumorigenesis is limited. This study investigated the appearance of 4-HNE-protein adducts in prostate cancer tissue by immunohistochemistry using a genuine 4-HNE monoclonal antibody. Plasma samples of the same patients and samples of the healthy controls were also analyzed for the presence of 4-HNE-protein adducts, followed by metabolic profiling using LC-ESI-QTOF-MS and GC-EI-Q-MS. Finally, the analysis of the metabolic pathways affected by 4-HNE was performed. The obtained results revealed the absence of 4-HNE-protein adducts in prostate carcinoma tissue but increased 4-HNE-protein levels in the plasma of these patients. Metabolomics revealed a positive association of different long-chain and medium-chain fatty acids with the presence of prostate cancer. Furthermore, while linoleic acid positively correlated with the levels of 4-HNE-protein adducts in the blood of healthy men, no correlation was obtained for cancer patients indicating altered lipid metabolism in this case. The metabolic pathway of unsaturated fatty acids biosynthesis emerged as significantly affected by 4-HNE. Overall, this is the first study linking 4-HNE adduction to plasma proteins with specific alterations in the plasma metabolome of prostate cancer patients. This study revealed that increased 4-HNE plasma protein adducts could modulate the unsaturated fatty acids biosynthesis pathway. It is yet to be determined if this is a direct result of 4-HNE or whether they are produced by the same underlying mechanisms. Further mechanistic studies are needed to grasp the biological significance of the observed changes in prostate cancer tumorigenesis