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Aging-related changes in oxidative stress response of human endothelial cells
Full text linkBACKGROUND: Oxidative stress is strongly associated with aging and age-related diseases and plays a crucial role in endothelial dysfunction development.
AIM: To better understand the molecular mechanisms of aging and stress response in humans, we examined changes to young and older human endothelial cells over time (72, 96 and 120 h), before and after H2O2-induced stress.
METHODS: We measured the expression of the deacetylase Sirtuin 1 (Sirt1) and its transcriptional target Forkhead box O3a (Foxo3a); TBARS, a well-known marker of overall oxidative stress, and catalase activity as index of antioxidation. Moreover, we quantified levels of cellular senescence by senescence-associated β galactosidase (SA-βgal) assay.
RESULTS: Under oxidative stress induction older cells showed a progressive decrease of Sirt1 and Foxo3a expression, persistently high TBARS levels with high, but ineffective Cat activity to counteract such levels. In addition cellular senescence drastically increased in older cells compared with Young cells both in presence and in the absence of oxidative stress.
DISCUSSION: By following the cell behavior during the time course, we can hypothesize that while in young cells an oxidative stress induction stimulated an adequate response through activation of molecular factor crucial to counteract oxidative stress, the older cells are not able to adequately adapt themselves to external stress stimuli.
CONCLUSIONS: During their life, endothelial cells impair the ability to defend themselves from oxidative stress stimuli. This dysfunction involves the pathway of Sirt1 a critical regulator of oxidative stress response and cellular lifespan, underlining its crucial role in endothelial homeostasis control during aging and age-associated diseases
[Sulphureous mud-bath therapy and changes in blood pressure: observational investigation]
No full textThe chronic arthropathies currently appear to be a major cause of disability with a negative impact on quality of life and health care spending. The mud-bath therapy is a spa treatment that induces benefic effects in chronic rheumatic diseases. It has long been debated on the assumption that the mud-bath spa therapy could have adverse cardiovascular effects which often induce caution and even a contraindication to the use of this treatment in chronic arthropathies associated with cardiovascular alterations such as hypertension. The aim of this observational study was to investigate, in arthrorheumatic subjects, the effects of sulphureous mud-bath cycle on blood pressure and the possible appearance of adverse drug reaction
Sirtuins: Possible Clinical Implications in Cardio and Cerebrovascular Diseases
No full textMammalian sirtuins (SIRT1-7) are NAD+-dependent deacetylases, which play an important role in aging and in a wide range of cellular functions. SIRT1, the best-characterized member of the family, acts as a sensor of the redox state and triggers in the cell the appropriate defense response. A large body of evidence has showed that SIRT1 induces both cellular and systemic protective effects in the cardiovascular system by preventing stress-induced apoptosis and senescence, and mitigating endothelial dysfunction. Hence, SIRT1 is now foreseen as a potential therapeutic target for a growing number of cardiovascular diseases. Recently, it has been suggested that SIRT1 activation could also be considered as a neuroprotective strategy. Indeed, SIRT1 protects against ischemia/reperfusion injury both in vitro and in vivo and avoids severe ischemic damage by preserving cerebral blood flow. In the last years it was suggested that others sirtuins, in particular SIRT3 and SIRT6, could exert beneficial effects in vascular syndromes. The aim of this review was to describe and discuss recent experimental evidence on the effects of SIRT1 and other sirtuins on the pathophysiology of cardio- and cerebrovascular diseases, underlying a potential therapeutic effect of these enzymes in the treatment and/or prevention of such conditions
Aerobic Training Workload Affects Human Endothelial Cells Redox Homeostasis.
No full textPURPOSE: Moderate aerobic exercise reduces oxidative stress, intense physical activity may produce the opposite result. At present, the effects of different exercise loads on oxidative stress markers and the response of human cells to different exercise volumes have not been fully elucidated.
METHODS: Human (Eahy-926) endothelial cells (ECs), exposed or not exposed to oxidative stress, were conditioned with sera from two groups of triathletes practising at different workloads.
RESULTS: Although no differences in functional and hemodynamic variables were observed between the two groups of triathletes, significant changes in some markers for oxidative stress were found in their sera. Thiobarbituric acid reactive substances (TBARS) and superoxide dismutase (SOD) activity were similar, but triathletes practicing the sport at lower volume (T1) had higher serum Nitric Oxide (NO) and lower catalase activity than triathletes performing the training at greater load (T2). The ECs conditioned with serum from T1 (T1-ECs) showed higher survival and proliferation rates and lower senescence levels than the ECs supplemented with T2 (T2-ECs) serum both before and after oxidative stress induction. These effects depended on catalase as demonstrated via enzyme activity inhibition using 3-amino-1,2,4-triazole (ATZ). After oxidative stress induction, Sirt1 activity, a regulator of the oxidative stress response, was significantly increased in the T1-ECs but not in the T2-ECs. Moreover, the T1-ECs required less catalase activity than the T2-ECs to counteract an equal amount of oxidative stress after H2O2 administration.
CONCLUSION: This study demonstrates that the beneficial effects of aerobic exercise are eliminated when the training is performed at a greater workload. Moreover, we suggest an oxidative stress marker, serum catalase activity, as a valid tool to use in the supervision of changes to exercise volume
Adrenergic signaling and oxidative stress: a role for sirtuins?
Full text linkThe adrenergic system plays a central role in stress signaling and stress is often associated with increased production of ROS. However, ROS overproduction generates oxidative stress, that occurs in response to several stressors. β-adrenergic signaling is markedly attenuated in conditions such as heart failure, with downregulation and desensitization of the receptors and their uncoupling from adenylyl cyclase. Transgenic activation of β2-adrenoceptor leads to elevation of NADPH oxidase activity, with greater ROS production and p38MAPK phosphorylation. Inhibition of NADPH oxidase or ROS significantly reduced the p38MAPK signaling cascade. Chronic β2-adrenoceptor activation is associated with greater cardiac dilatation and dysfunction, augmented pro-inflammatory and profibrotic signaling, while antioxidant treatment protected hearts against these abnormalities, indicating ROS production to be central to the detrimental signaling of β2-adrenoceptors. It has been demonstrated that sirtuins are involved in modulating the cellular stress response directly by deacetylation of some factors. Sirt1 increases cellular stress resistance, by an increased insulin sensitivity, a decreased circulating free fatty acids and insulin-like growth factor (IGF-1), an increased activity of AMPK, increased activity of PGC-1a, and increased mitochondrial number. Sirt1 acts by involving signaling molecules such P-I-3-kinase-Akt, MAPK and p38-MAPK-β. βAR stimulation antagonizes the protective effect of the AKT pathway through inhibiting induction of Hif-1α and Sirt1 genes, key elements in cell survival. More studies are needed to better clarify the involvement of sirtuins in the β-adrenergic response and, overall, to better define the mechanisms by which tools such as exercise training are able to counteract the oxidative stress, by both activation of sirtuins and inhibition of GRK2 in many cardiovascular conditions and can be used to prevent or treat diseases such as heart failure
A Prospective Screening of HLA-B*57.01 Allelic Variant for Preventing the Hypersensivity Reaction to Abacavir: Experience from the Laboratory of Molecular Biology of the Infectious Diseases Division at the University Hospital of Salerno
No full textAbacavir is a nucleoside reverse transcriptase inhibitor largely used as part of the antiretroviral therapy in Human Immunodeficiency Virus (HIV)-infected patients. Some individuals (2-9%) who start an abacavir treatment show an immunologic reaction indicated as hypersensitivity reaction syndrome (HSR) that is often responsible for therapy discontinuation and could represent a life-threatening event. Some studies demonstrated a correlation between this adverse reaction and the class I of the major histocompatibility complex (MHC) allele, HLA-B*57.01, in several populations, including Caucasians. Nowadays, International HIV treatment guidelines recommend the HLA-B*57.01 genotyping before abacavir administration to reduce the incidence of HSR. Both male and female HIV-infected patients were enrolled at the Infectious Diseases Division at the University Hospital of Salerno, and admitted to a prospective HLAB*57.01 screening. Genetic analysis was carried out through two sequential Real-Time PCR reactions in which Sybr-Green was used. Out of 248 patients, 215 were Italians from Southern Italy and 33 were coming from several non-EU members countries. All were genotyped: 6 Italians (2.8%) and 1 of the non-EU group (3%) were identified as HLAB*57.01 carriers. In this paper we present our experience in the field of abacavir pharmacogenetic and confirm the importance of Real Time PCR as a valid and cost-effective HLA-B*57.01 typing methodology
Aerobic training workload affects human endothelial cells redox homeostasis
No full textPURPOSE: Moderate aerobic exercise reduces oxidative stress, whereas intense physical activity may produce the opposite result. At present, the effects of different exercise loads on oxidative stress markers and the response of human cells to different exercise volumes have not been fully elucidated.
METHODS: Human (Eahy-926) endothelial cells (EC), exposed or not exposed to oxidative stress, were conditioned with sera from two groups of triathletes practicing at different workloads.
RESULTS: Although no differences in functional and hemodynamic variables were observed between the two groups of triathletes, significant changes in some markers for oxidative stress were found in their sera. Thiobarbituric acid reactive substances and superoxide dismutase activity were similar, but triathletes practicing the sport at lower volume (T1) had higher serum nitric oxide and lower catalase activity than triathletes performing the training at greater load (T2). The EC conditioned with serum from T1 (T1-EC) showed higher survival and proliferation rates and lower senescence levels than the EC supplemented with T2 (T2-EC) serum both before and after oxidative stress induction. These effects depended on catalase as demonstrated via enzyme activity inhibition using 3-amino-1,2,4-triazole. After oxidative stress induction, Sirt1 activity, a regulator of the oxidative stress response, was significantly increased in the T1-EC but not in the T2-EC. Moreover, the T1-EC required less catalase activity than the T2-EC to counteract an equal amount of oxidative stress after H2O2 administration.
CONCLUSION: This study demonstrates that the beneficial effects of aerobic exercise are eliminated when the training is performed at a greater workload. Moreover, we suggest an oxidative stress marker, serum catalase activity, as a valid tool to use in the supervision of changes to exercise volume
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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