P53 Regulation upon Lipid Peroxidation and Ferroptosis for Intervention against Atherogenesis.

Tumor protein 53 (P53), as an intracellular regulator of antioxidant responses, participates in the expression of antioxidant defense and lipid metabolism as well as the synthesis of genes in cells. The balance of oxidation and reduction can be disrupted by many pathological conditions, and the role of the antioxidant system in protecting the equilibrium state from pathological effects, such as reactive lipids, is crucial. In particular, the excessive accumulation of lipid peroxidation products is a key factor driving the occurrence and development of various diseases. Ferroptosis is an iron-dependent, lipid peroxidation-driven cell death cascade reaction, which has become a key research area in cardiovascular diseases. Atherosclerosis (AS) is a pathological change caused by lipid metabolic disorder, inflammatory response, and endothelial cell injury, and is the most common cause of cardiovascular disease. This review briefly outlines lipid peroxidation and key components involving ferroptosis cascade reactions, summarizes and emphasizes the role of P53-related signaling pathways in mediating lipid peroxidation and ferroptosis, and focuses on the known P53 target genes that regulate these pathways, as well as explores the possibility of P53 intervention in the treatment of AS by regulating lipid peroxidation and ferroptosis processes.

Protective Mechanism of Humanin Against Oxidative Stress in Aging-Related Cardiovascular Diseases.

Physiological reactive oxygen species (ROS) are important regulators of intercellular signal transduction. Oxidative and antioxidation systems maintain a dynamic balance under physiological conditions. Increases in ROS levels destroy the dynamic balance, leading to oxidative stress damage. Oxidative stress is involved in the pathogenesis of aging-related cardiovascular diseases (ACVD), such as atherosclerosis, myocardial infarction, and heart failure, by contributing to apoptosis, hypertrophy, and fibrosis. Oxidative phosphorylation in mitochondria is the main source of ROS. Increasing evidence demonstrates the relationship between ACVD and humanin (HN), an endogenous peptide encoded by mitochondrial DNA. HN protects cardiomyocytes, endothelial cells, and fibroblasts from oxidative stress, highlighting its protective role in atherosclerosis, ischemia-reperfusion injury, and heart failure. Herein, we reviewed the signaling pathways associated with the HN effects on redox signals, including Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2), chaperone-mediated autophagy (CMA), c-jun NH2 terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38 MAPK), adenosine monophosphate-activated protein kinase (AMPK), and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)-Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3). Furthermore, we discussed the relationship among HN, redox signaling pathways, and ACVD. Finally, we propose that HN may be a candidate drug for ACVD.

Redox toxicology of environmental chemicals causing oxidative stress.

Living organisms are surrounded with heavy metals such as methylmercury, manganese, cobalt, cadmium, arsenic, as well as pesticides such as deltamethrin and paraquat, or atmospheric pollutants such as quinone. Extensive studies have demonstrated a strong link between environmental pollutants and human health. Redox toxicity is proposed as one of the main mechanisms of chemical-induced pathology in humans. Acting as both a sensor of oxidative stress and a positive regulator of antioxidants, the nuclear factor erythroid 2-related factor 2 (NRF2) has attracted recent attention. However, the role NRF2 plays in environmental pollutant-induced toxicity has not been systematically addressed. Here, we characterize NRF2 function in response to various pollutants, such as metals, pesticides and atmospheric quinones. NRF2 related signaling pathways and epigenetic regulations are also reviewed.

Potential effects of noxious chemical-containing fine particulate matter on oral health through reactive oxygen species-mediated oxidative stress: Promising clues.

Nowadays, air pollution which is dominated by fine particulate matter with aerodynamic diameter less than or equal to 2.5 µm resulting from rapid industrialization and urbanization combined with population explosion has become more and more severe problem to mankind and the whole planet because of its diversity of deleterious effects. The latest data estimated that exposure to fine particulate matter, or PM2.5, contributes to approximately 4 million deaths worldwide due to cardiopulmonary conditions such as heart disease and stroke, respiratory infections, chronic lung disease and lung cancer. During recent years, there has been growing concern about the adverse effects of this global threat on oral health which is one of key components of general health and quality of life. Although a few studies have reported such possible association, the findings are still far from conclusion. Moreover, the underlying mechanisms remain unclear. To our knowledge, the analysis of literature regarding this scope has yet been published. Thus, current work systematically assesses existing evidences on the potential association between exposure to PM2.5 and the development of various oral diseases as well as figures out the plausible paradigm of PM2.5-induced damages in the oral cavity through its toxic chemical constituents along with its ability to induce oxidative stress via reactive oxygen species production. This might partially provide the clues for new research ideas and progression in the field of oral health.

The Inducible Role of Ambient Particulate Matter in Cancer Progression via Oxidative Stress-Mediated Reactive Oxygen Species Pathways: A Recent Perception.

Cancer is one of the leading causes of premature death and overall death in the world. On the other hand, fine particulate matter, which is less than 2.5 microns in aerodynamic diameter, is a global health problem due to its small diameter but high toxicity. Accumulating evidence has demonstrated the positive associations between this pollutant with both lung and non-lung cancer processes. However, the underlying mechanisms are yet to be elucidated. The present review summarizes and analyzes the most recent findings on the relationship between fine particulate matter and various types of cancer along with the oxidative stress mechanisms as its possible carcinogenic mechanisms. Also, promising antioxidant therapies against cancer induced by this poison factor are discussed.

Angiotensin II and leukocyte trafficking: New insights for an old vascular mediator. Role of redox-signaling pathways.

Inflammation and activation of the immune system are key molecular and cellular events in the pathogenesis of cardiovascular diseases, including atherosclerosis, hypertension-induced target-organ damage, and abdominal aortic aneurysm. Angiotensin II (Ang-II) is the main effector peptide hormone of the renin-angiotensin system. Beyond its role as a potent vasoconstrictor and regulator of blood pressure and fluid homeostasis, Ang-II is intimately involved in the development of vascular lesions in cardiovascular diseases through the activation of different immune cells. The migration of leukocytes from circulation to the arterial subendothelial space is a crucial immune response in lesion development that is mediated through a sequential and coordinated cascade of leukocyte-endothelial cell adhesive interactions involving an array of cell adhesion molecules present on target leukocytes and endothelial cells and the generation and release of chemoattractants that activate and guide leukocytes to sites of emigration. In this review, we outline the key events of Ang-II participation in the leukocyte recruitment cascade, the underlying mechanisms implicated, and the corresponding redox-signaling pathways. We also address the use of inhibitor drugs targeting the effects of Ang-II in the context of leukocyte infiltration in these cardiovascular pathologies, and examine the clinical data supporting the relevance of blocking Ang-II-induced vascular inflammation.

Oxidative stress, redox signaling pathways, and autophagy in cachectic muscles of male patients with advanced COPD and lung cancer.

Muscle dysfunction and wasting are predictors of mortality in advanced COPD and malignancies. Redox imbalance and enhanced protein catabolism are underlying mechanisms in COPD. We hypothesized that the expression profile of several biological markers share similarities in patients with cachexia associated with either COPD or lung cancer (LC). In vastus lateralis of cachectic patients with either LC (n=10) or advanced COPD (n=16) and healthy controls (n=10), markers of redox balance, inflammation, proteolysis, autophagy, signaling pathways, mitochondrial function, muscle structure, and sarcomere damage were measured using laboratory and light and electron microscopy techniques. Systemic redox balance and inflammation were also determined. All subjects were clinically evaluated. Compared to controls, in both cachectic groups of patients, a similar expression profile of different biological markers was observed in their muscles: increased levels of muscle protein oxidation and ubiquitination (p<0.05, both), which positively correlated (r=0.888), redox-sensitive signaling pathways (NF-κB and FoxO) were activated (p<0.05, all), fast-twitch fiber sizes were atrophied, muscle structural abnormalities and sarcomere disruptions were significantly greater (p<0.05, both). Structural and functional protein levels were lower in muscles of both cachectic patient groups than in controls (p<0.05, all). However, levels of autophagy markers including ultrastructural autophagosome counts were increased only in muscles of cachectic COPD patients (p<0.05). Systemic oxidative stress and inflammation levels were also increased in both patient groups compared to controls (p<0.005, both). Oxidative stress and redox-sensitive signaling pathways are likely to contribute to the etiology of muscle wasting and sarcomere disruption in patients with respiratory cachexia: LC and COPD.