Nitric oxide and oxidative stress in cardiovascular aging

The long-standing free radical theory of aging, which attributes cellular pathology to the relentless accumulation of reactive oxygen species (ROS), remains attractive but controversial. Emerging insights into the molecular interactions between ROS and reactive nitrogen species (RNS) such as nitric oxide suggest that, in biological systems, one effect of increased ROS is the disruption of protein S-nitrosylation, a ubiquitous posttranslational modification system. In this way, ROS may not only damage cells but also disrupt widespread signaling pathways. Here, we discuss this phenomenon in the context of the cardiovascular system and propose that ideas regarding oxidative stress and aging need to be reevaluated to take account of the balance between oxidative and nitrosative stress.     

The Levels of Cortisol,Oxidative Stress,and DNA Damage in the Victims of Childhood Sexual Abuse: A Preliminary Study

In this study we aimed to investigate serum cortisol, oxidative stress, and DNA damage in children who are sexual abuse victims. The study included 38 children who sustained child sexual abuse and 38 age- and gender-matched children who did not have a history of trauma. Cortisol levels reflecting the status of the hypothalamic-pituitary-adrenal axis, anti-oxidant enzymes glutathione peroxidase, superoxide dismutase, natural anti-oxidant coenzyme Q, and 8-hydroxy-2-deoxyguanosine as the indicator of DNA damage were analyzed in serum samples using the enzyme linked immunosorbent assay method. Cortisol levels were significantly higher in the child sexual abuse group compared to the control group. There were no significant differences between the groups in terms of oxidative stress and DNA damage. Cortisol and 8-hydroxy-2-deoxyguanosine levels decreased as the time elapsed since the sexual abuse increased. Coenzyme Q level was lower in victims who sustained multiple assaults than in the victims of a single assault. Cortisol and superoxide dismutase levels were lower in the victims of familial sexual abuse. Decreases in cortisol and 8-hydroxy-2-deoxyguanosine levels as time elapsed may be an adaptation to the toxic effects of high cortisol levels over a prolonged period of time. Child sexual abuse did not result in oxidative stress and DNA damage; however, some features of sexual abuse raised the level of oxidative stress.     

Gender-dependent variations in systemic biomarkers of oxidative protein,DNA, and lipid damage in aged rats

Introduction.?The effect of aging on plasma-protein, lipid and DNA oxidation is well documented. However, none of the studies specify the effect of gender. The purpose of this study is to clarify the ambiguity raised in preliminary reports as to gender dependency of oxidative damage in plasma.

Methods.?In the current study, we investigated the relation between 8-hydroxy-2′-deoxyguanosine levels (8-OHdG), which is a measure of DNA oxidation and protein oxidation parameters such as protein carbonyl (PCO), total thiol (T-SH), and advanced oxidation protein products (AOPP). Our study also covered other oxidative stress parameters, such as lipid hydroperoxides (LHP), malondialdehyde (MDA), erythrocyte glutathione (GSH), superoxide dismutase (Cu-Zn SOD) and the catalase (CAT) activity in plasma of the male and female aged rats.

Results.?8-OHdG and MDA levels in male rats were significantly higher than those in the female group (p?<?0.01 for both parameters). T-SH levels were found to be higher in female rats than in the male (p?<?0.05). Plasma Cu-Zn SOD activities of male rats were significantly higher compared with those of the female rats (p?<?0.05). On the other hand, PCO, AOPP, LHP, GSH levels, and CAT activity were not found to be different between genders.

Conclusions.?We suggest that increased T-SH levels found in female rats may point to an adaptive reaction to oxidative damage, reflecting 8-OHdG and MDA overproduction. We are of the conviction that the increased 8-OHdG and MDA that we have determined in aged male rats may be a risk factor in the extent of oxidation in plasma.     

Structure-(Dys)function relationships in mitochondrial electron transport chain complex II?

It has been postulated that mitochondrially derived reactive oxygen species (ROS) play a major causative role in aging processes. The primary sources of these oxidants are believed to be complexes I and III of the electron transport chain, with little evidence supporting oxidant formation at complex II (succinate dehydrogenase). Mutation of a complex II protein has, however, been shown to cause increased oxidative stress and decreased life expectancy in the Caenorhabditis elegans mutant mev-1. A recent study by Yankovskaya and colleagues, in which the structure of Escherichia coli succinate dehydrogenase was determined, provides an explanation for these observations. Furthermore, these results suggest possible mechanisms by which electron leakage might occur at this site in the aged organism.     

Carnosine: a versatile antioxidant and antiglycating agent

Carnosine (beta-alanyl-L-histidine) has recently attracted much attention as a naturally occurring antioxidant and transition-metal ion sequestering agent. It has also been shown to act as an anti-glycating agent, inhibiting the formation of advanced glycation end products (AGEs). Through its distinctive combination of antioxidant and antiglycating properties, carnosine is able to attenuate cellular oxidative stress and can inhibit the intracellular formation of reactive oxygen species and reactive nitrogen species. By controlling oxidative stress, suppressing glycation, and chelating metal ions, carnosine is able to reduce harmful sequelae such as DNA damage. AGEs are known contributors to the pathology of Alzheimer's disease, and carnosine therefore merits serious attention as a possible therapeutic agent.     

Lipid peroxidation and the aging process

Consistent evidence supports the hypothesis that a progressive accumulation of oxidative damage to important cellular molecules is a fundamental mechanism involved in most senescence-associated alterations. Oxidative damage occurs when free radicals produced within an organism are not completely destroyed by the appropriate endogenous defense systems. Because lipids are a major component of living organisms and probably the first easy target of free radicals once they are produced, lipid peroxidation might play an important role in initiating and/or mediating some aspects of the aging process. It has been widely demonstrated that there is an age-associated increase in the steady-state concentrations of lipid peroxidation products. However, establishing the involvement of this phenomenon in the pathogenesis of the aging process has not been an easy task. The recent development of more reliable techniques to measure lipid peroxidation, together with more well-defined animal models of aging, should be of great help in future studies in this field. The current evidence for the presence and importance of lipid peroxidation in the aging process is discussed in this review.     

Oxidative mutagenesis, mismatch repair, and aging

A PubMed search for the term "oxidative stress" yields over 29,000 articles published on the subject over the past 10 years; more than 2000 of these articles also include the term "aging" in their title or abstract. Many theories of aging predict causal roles for oxidative stress in the myriad of pathological changes that occur as a function of age, including an increasing propensity to develop cancer. A possible link between aging and cancer is the induction and accumulation of somatic mutations caused by oxidative stress. This Review focuses on small mutational events that are induced by oxidative stress and the role of mismatch repair (MMR) in preventing their formation. It also discusses a possible inhibitory effect of oxidative stress on MMR. We speculate that a synergistic interaction between oxidative damage to DNA and reduced MMR levels will, in part, account for an accumulation of small mutational events, and hence cancer, with aging.     

The two faces of oxygen

Scientists have suspected for half a century that reactive oxygen species (ROS) are major instigators of aging. These byproducts of metabolism batter a wide variety of molecules within cells, and an organism's ability to repair the damage declines with age. Now, some researchers say they're wrapping up the case against ROS, at least for lower organisms. By counteracting this destruction with protective enzymes, researchers have extended the average lifetime of some invertebrates. But the verdict isn't in yet, because recent studies have revealed that ROS also make key contributions to normal cell signaling.     

Determination of oxidative stress levels and some antioxidant enzyme activities in prostate cancer

In this study, the antioxidant enzyme activities such as (SOD, GSH, and CAT) and malondialdehyde (MDA) level which is the end product of lipid peroxidation, were determined from the serum samples taken from patients diagnosed with prostate cancer Van Yuzuncu Y?l University Medical Faculty of Educational Research and Training Hospital and ?stanbul Bagcilar Education Research Hospital. The SOD, GSH, and CAT activity of patient groups was found significantly lower than the healthy control group in patients with prostate cancer (p?相似文献   

Exploiting proteomics in the discovery of drugs that target mitochondrial oxidative damage

To understand how oxidative stress contributes to aging and age-related diseases and to better evaluate the therapeutic effect of antioxidant drugs, it would be highly desirable to have a comprehensive and detailed readout of the types of oxidative damage that occur to proteins at a global or proteome level. In this Perspective, I examine how proteomics, defined here as the science of examining all proteins in an organelle, cell, or tissue in the context of biological phenomena, can be used to provide molecular details of mitochondrial protein oxidative damage. Specifically, I discuss approaches that combine knowledge of the mitochondrial proteome with newer mass spectrometry-based techniques that are capable of identifying proteins and sites of oxidative modification in a high-throughput manner.     

Mouse and human cells versus oxygen

Mice and humans are at opposite ends of the mammalian spectrum of longevity. A major question in biology is whether this difference can be accounted for by differences in the properties of cells from these two species. A new publication from Judith Campisi's lab reports that human cells in culture are more resistant than mouse cells to the damaging effects of 20% oxygen. The greater burden of DNA damage sustained by mouse cells causes them to rapidly enter a phase of culture in which most cells enter permanent growth arrest (replicative senescence). However, some mouse cells usually escape from senescence and then grow into an immortal cell line. This never happens in human fibroblast cell cultures. Human cells also eventually enter replicative senescence in culture, but this phenomenon is caused by shortening of telomeres and not by DNA damage of the type responsible for mouse cell senescence. Human fibroblasts never spontaneously escape from senescence. This Perspective reviews differences between mouse and human cells that could account for these differences in behavior. Some evidence indicates that human cells are generally more resistant than mouse cells to oxidative damage to DNA, but more needs to be done to confirm this finding and to understand the underlying mechanisms. Whether or not there are differences in the amount of DNA damage caused by oxygen or in the early phase of repair, there may be important differences in the later consequences of DNA damage. Mouse cells appear to be able to continue to divide with DNA damage that has not been repaired or has been misrepaired, and becomes fixed in the form of chromosomal abnormalities. The checkpoints that cause cells to stop dividing when chromosomes develop abnormalities (aberrations or shortened telomeres) appear to operate more efficiently in human cells. Much more work is needed to understand the basis for these differences and the implications for aging and cancer.     

There's a problem in the furnace

A long-sought-after mutation in the manganese superoxide dismutase gene MnSOD has been isolated in Drosophila melanogaster. The MnSOD null mutation is recessive lethal, with death occurring just after eclosion. In this Perspective, I discuss these results and related work in mice within the context of the oxidative damage theory of aging.     

The effects of ROS in prostatic stromal cells under hypoxic environment

Abstract

Objective: The objective of this study is to explore the effects of reactive oxygen species (ROS) under hypoxic environment in prostatic stromal cells (PSC).

Methods and materials: To detect the expression of ROS in PSC and the tissues of benign prostatic hyperplasia (BPH) by flow cytometry; under hypoxic conditions, to observe the changes of cells growth and ROS in PSC; quantitative PCR was used to detect hypoxia inducible factor-1α (HIF-1α), androgen receptors (AR), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) in PSC; After edaravone intervening, to examine the changes of cells growth, ROS, HIF-1α, AR, VEGF, and IL-8 under hypoxic conditions.

Results: The expression of ROS in tissues and cells which under hypoxic condition was significantly increased. 3% O₂ promoted the proliferation. The HIF-1α, AR, VEGF, and IL-8 were upregulated under 3% O₂. After edaravone intervening, ROS significantly decreased, HIF-1α and VEGF were downregulated, and cell proliferation declined.

Conclusions: Hypoxia stimulates the generation of ROS, and the ROS may play a key role in BPH.     

Oxidative stress increases continuously with BMI and age with unfavourable profiles in males

Oxidative stress is a risk factor for chronic diseases and was previously shown to be independently associated with obesity. The authors investigated the relationship between body mass index (BMI), age and oxidative stress on 2190 subjects undergoing a health care examination. Total antioxidant status (TAS), total peroxides (TOC) and autoantibodies against oxidized LDL (oLAb) were used as oxidative stress biomarkers in addition to serum lipoproteins, bilirubin and uric acid. Gender-specific differences were observed for age, BMI, serum concentrations of bilirubin, low-density lipoprotein (LDL), uric acid and TAS, all of which were higher in males (p < 0.001), while high-density lipoprotein (HDL), HDL/LDL ratio and TOC were higher in females (p < 0.001). Total cholesterol (p < 0.05) and LDL were increased (p < 0.05), while HDL was decreased (p < 0.05) in overweight and obese subjects. This was accompanied by increased uric acid and TAS concentrations. Lowest oLAb titers were detected in obese subjects. In extremely obese subjects, increased TOC and decreased TAS were observed in spite of high uric acid levels. These results demonstrate that oxidative stress increases with increasing BMI and age, as a sequel to an impaired antioxidant status, the consumption of oLAbs, an increase of peroxides and uric acid and a disadvantaged lipid profile.     

Nepenthe Theory of Defense Mechanism Functioning and Defensive Behavior in African-U.S. People With Replication and Extension to Psychological Africanity (Racial Identity)

Ego mechanisms of defense were studied in a sample of 140 African-U.S. college students using for theoretical approaches Michael Bond’s defense style hierarchy and Daudi Ajani ya Azibo’s nepenthe theory. Each framework was supported in the data. Also, previous findings from an earlier exploratory study were replicated including greater defense style scoring compared to Caucasian norms and association between defense style scores and depression. In addition, this study incorporated measures of normal and abnormal psychological Africanity (racial identity). Defense style scores predicted indices of psychopathologic psychological Africanity (African-U.S. culture?focused mental disorders). Own-race negation and abjuration indices predicted defense style scores. ANOVAs found highest defense style scores for participants classified as having correct psychological Africanity orientation (highest psychological Africanity/racial identity scores) compared to diffused and incorrect lower classifications. It was concluded that the study of defensive behavior among African-U.S. persons might be tempered by nepenthe theory.     

Our common future: a rapidly growing and rapidly aging humankind

Abstract

Physical inactivity, diabetes, hypertension, dyslipidemia, smoking and obesity were associated with imbalance in oxidative stress, leading to endothelial dysfunction. Such dysfunction is present in both cardiovascular disease (CVD) and erectile dysfunction (ED). ED is the persistent inability to achieve or sustain an erection sufficient for satisfactory sexual performance and is one of the first manifestations of endothelial damage in men with CVD risk factors. The purpose of this article is to review the results of studies involving physical activity, CVD, endothelial dysfunction and ED in order to verify its applicability for improving the health and quality of life of men with such disorders. There is consistent evidence that endothelial damage is intimately linked to ED, and this manifestation seems to be associated with the appearance CVDs. On the other hand, physical activity has been pointed out as an important clinical strategy in the prevention and treatment of CVDs and ED mainly associated with improvement of endothelial function. However, further experimental and clinical prospective investigations are needed to test the role of physical exercises in the modulation of endothelial function and their implications on erectile function and the appearance of CVDs.     

Reactive oxygen species and aging: evolving questions

Over the past 50 years, reactive oxygen species (ROS) have been investigated as putative mediators of the process of aging. As specific genes and pathways that are involved with ROS homeostasis have been linked to aging in lower organisms, such as Caenorhabditis elegans and Drosophila, the questions of how ROS regulate aging in higher organisms, and whether they do so to the same extent as in lower organisms, have emerged.     

Repression and other Forms of Cognitive Evasiveness: Implications for Stress Symptoms in College Students

Abstract

Lazarus has proposed that palliative defenses against threat that interfere with direct efforts to alleviate the threat may prove maladaptive. Three evasive cognitive attributes that circumvent awareness of threat were studied to determine whether they related to the prevalence of stress symptoms in college students. Repression (selective forgetting of threatening material), awareness of the repressive defense, and internal scanning (breadth of association to cues) were considered. College students of both sexes who engaged in evasive cognitive activity reported more stress symptoms than those who did not, with a progressive increase in stress as increasingly homogeneous groups were considered. Students who defended themselves by repression experienced more stress than those who did not. Repressors who were the least aware of their use of this defense reported even more stress. Unconscious repressors who were the least reflective (narrow scanners) showed the highest frequency of stress symptoms.     

Lessons from Drosophila models of DJ-1 deficiency

Mutations in the DJ-1 gene are associated with rare forms of autosomal recessive early-onset Parkinson's disease (PD). Although the precise physiological function of DJ-1 remains obscure, accumulating evidence suggests that DJ-1 may normally function as a redox-sensitive molecular chaperone that can protect against the deleterious effects of oxidative stress, particularly in mitochondria. Recent studies in the fruit fly, Drosophila melanogaster, have shed further light on the biological role of DJ-1. DJ-1-deficient Drosophila models exhibit distinct phenotypes but collectively highlight a prominent neuroprotective role for DJ-1 against oxidative insult. However, Drosophila lacking DJ-1 do not consistently produce a useful PD-like phenotype (that is, they generally fail to exhibit degeneration of neurons that contain the neurotransmitter dopamine), which may reflect putative compensatory neuroprotective mechanisms. DJ-1-deficient fly models further highlight the utility of Drosophila as an important tool for elucidating protein function and for modeling neurodegenerative disease.     

Neuropathology in Alzheimer's disease: awaking from a hundred-year-old dream

For one hundred years after Alois Alzheimer's first report of Alzheimer's disease (AD) in 1906, the pathological hallmarks of the disease, senile plaques and neurofibrillary tangles (NFTs), have been attractive targets for researchers. Therefore, not surprisingly, efforts to understand disease mechanisms have concentrated on the cell biology of amyloid-beta (Abeta) deposition as senile plaques or on the phosphorylation and aggregation of tau as NFTs. However, it now appears that this focus on pathology as a central contributor to disease may be misguided. Indeed, neurons associated with Abeta and NFTs in AD brain show a decrease in oxidative damage relative to those in vulnerable but morphologically intact areas of the brain, suggesting that neurodegenerative lesions are compensatory phenomena, and thus manifestations of cellular adaptation. That Abeta and tau accumulations indicate an age-related physiological reaction to chronic stress calls into question the rationale of current therapeutic efforts targeted toward lesion removal. Moreover, if this concept holds true for pathology in other neurodegenerative diseases, we may need to restructure our thinking and undergo a paradigm shift before substantial progress can be made in therapeutic intervention.