AlphaB-crystallin and breast cancer Caporossi, Daniela; Parisi, Attilio; Fantini, Cristina ...
Cell stress & chaperones,
01/2021, Letnik:
26, Številka:
1
Journal Article
Recenzirano
Odprti dostop
AlphaB-crystallin (HSPB5) is one of the most prominent and well-studied members of the small heat shock protein (sHsp) family. To date, it is known that this protein modulates significant cellular ...processes and therefore, it is not surprising that its deregulation is involved in various human pathologies, including cancer diseases. Despite the pathogenic significance of HSPB5 in cancer and its regulatory mechanism related to aggressiveness is poorly understood, several reports describe the association of breast carcinoma progression with HSPB5, whose expression is also considered an independent predictor of breast cancer metastasis to the brain. Indeed, numerous authors indicate HSPB5 as a new valuable biomarker for clinicopathological parameters and poor prognosis in breast cancer. Considering the cytoprotective, anti-apoptotic, pro-angiogenic, and pro-metastatic properties of the sHsps, it is not surprising that they are considered as promising targets for anticancer treatment, even though, at present, a deeper understanding of their mode of action is needed to allow the development of precise therapeutic interventions. Data on the direct inhibition of different sHsps demonstrate promising results in cancer pathologies; however, specific strategies against HSPB5 have not been considered. This review highlights the most relevant findings on HSPB5 and its role in breast cancer, as well as the possible strategies in using HSPB5 inhibition for therapeutic purposes.
Strength training plays a crucial role in promoting healthy ageing and music might affect how individuals perform and perceive strength exercises. This study aimed to investigate the effects of ...self-selected music (SSM) on muscle strength and affective states during maximal isometric contractions on a customized leg extension.
Twenty-six healthy middle-aged males (50.8 ± 8.4 years) performed maximal and endurance isometric strength tests under three different conditions: SSM, motivational music (MM), and control condition (CC). Peak force and Rate of Force Development (RFD) were assessed during the maximal isometric strength test. The isometric endurance test evaluated the mean force and a fatigue index. Moreover, Felt Arousal Scale (FAS) was administered before the strength protocol, whereas the Rate of Perceived Exertion (RPE) and Feeling Scale (FS) at the end of it.
Mean force was significantly higher in the SSM (507.3 ± 132.2 N) than MM (476.3 ± 122.4 N,
< 0.01) and CC (484.6 ± 119.2 N,
= 0.03). FAS was significantly higher in the SSM (4.0 1.3 than MM (3.0 2.3,
< 0.01) and CC (3.0 1.3,
< 0.01) conditions. FS was significantly higher in the SSM (4.0 2.0 than MM (3.0 1.3,
< 0.01) and CC (3.0 1.3,
< 0.01) conditions. No significant differences were found for peak force, RFD, fatigue index, and RPE.
Listening to SSM seems to influence isometric endurance strength performance in middle-aged adults positively. Moreover, listening to SSM might improve individuals' affective states without affecting the level of perceived exertion.
The increase in breast cancer (BC) survival has determined a growing survivor population that seems to develop several comorbidities and, specifically, treatment-induced cardiovascular disease (CVD), ...especially those patients treated with anthracyclines. Indeed, it is known that these compounds act through the induction of supraphysiological production of reactive oxygen species (ROS), which appear to be central mediators of numerous direct and indirect cardiac adverse consequences. Evidence suggests that physical exercise (PE) practised before, during or after BC treatments could represent a viable non-pharmacological strategy as it increases heart tolerance against many cardiotoxic agents, and therefore improves several functional, subclinical, and clinical parameters. At molecular level, the cardioprotective effects are mainly associated with an exercise-induced increase of stress response proteins (HSP60 and HSP70) and antioxidant (SOD activity, GSH), as well as a decrease in lipid peroxidation, and pro-apoptotic proteins such as Bax, Bax-to-Bcl-2 ratio. Moreover, this protection can potentially be explained by a preservation of myosin heavy chain (MHC) isoform distribution. Despite this knowledge, it is not clear which type of exercise should be suggested in BC patient undergoing anthracycline treatment. This highlights the lack of special guidelines on how affected patients should be managed more efficiently. This review offers a general framework for the role of anthracyclines in the physio-pathological mechanisms of cardiotoxicity and the potential protective role of PE. Finally, potential exercise-based strategies are discussed on the basis of scientific findings.
Music is made up of several features (
., melody and rhythm) and it accompanies our life in different daily activities. During the last years, there was a growing interest in research about the ...music-related effects in the exercise domain. Music stimuli could act as an ergogenic effect leading to improvements in health-related and physical fitness components like cardiorespiratory endurance and muscular fitness. Moreover, listening to music may positively affect individuals' psychological state which could lead to increased exercise adherence. Conflicting data exist regarding the effects of music on cardiorespiratory and muscle-strengthening exercises indicating that music's characteristics (
., rhythm and musicality), studied samples (
., athletes and amateur) and methodology (
., self-selected music and research-selected music) might influence the results. Listening to music while exercising is becoming more frequent also in recreationally active individuals. While literature mainly focused on the effects of music in elite and amateur athletes, little data are available regarding recreationally active participants. Therefore, this review aims to summarize evidence regarding the effects of music on health-related physical fitness components in recreationally active individuals, specifically referring to cardiorespiratory endurance and muscular fitness. These outcomes will be helpful to all recreationally active participants to optimize the exercise protocol with the use of music.
The international literature emphasizes the importance of physical activity (PA) in the first steps after cancer surgery. The regular practice of physical exercise causes positive adaptations on ...several functional capacities, with positive consequences on patients' quality of life. This project aims to evaluate the effect of a post-operative training protocol, structured by taking into account both cancer-related issues and the presence of comorbidities, on functional capacities and quality of life of breast cancer survivors. Therefore, it was necessary to create a synergy between oncologists (referring physicians), sport medicine physicians (risk stratification and exercise prescription) and kinesiologists (trainers). Thirty-five post-surgery BC patients decided on a voluntary basis to attend an online Adapted PA (APA) protocol for 4 months, twice a week (APA Group) or Usual Care Group (UC Group). Functional capacity of the APA Group significantly increased, by 13.1% (
= 0.000), whereas perceived exertion decreased by 19.7% (
= 0.020). In the same group, the general health evaluated through the questionnaire EORTC-QLQ-C30 increased (
= 0.050). No differences were found in the UC Group. Operation Phalco, creating a network between oncologists, sports medicine physicians and kinesiologists, confirms the importance of structuring a post-operative path where APA should be included as early as possible in the cancer patient care.
Most anticancer treatments act on oxidative-stress pathways by producing reactive oxygen species (ROS) to kill cancer cells, commonly resulting in consequential drug-induced systemic cytotoxicity. ...Physical activity (PA) has arisen as an integrative cancer therapy, having positive health effects, including in redox-homeostasis. Here, we investigated the impact of an online supervised PA program on promoter-specific DNA methylation, and corresponding gene expression/activity, in 3 antioxidants- (SOD1, SOD2, and CAT) and 3 breast cancer (BC)-related genes (BRCA1, L3MBTL1 and RASSF1A) in a population-based sample of women diagnosed with primary BC, undergoing medical treatment. We further examined mechanisms involved in methylating and demethylating pathways, predicted biological pathways and interactions of exercise-modulated molecules, and the functional relevance of modulated antioxidant markers on parameters related to aerobic capacity/endurance, physical fatigue and quality of life (QoL).
PA maintained levels of SOD activity in blood plasma, and at the cellular level significantly increased SOD2 mRNA (≈+77 %), contrary to their depletion due to medical treatment. This change was inversely correlated with DNA methylation in SOD2 promoter (≈−20 %). Similarly, we found a significant effect of PA only on L3MBTL1 promoter methylation (≈−25 %), which was inversely correlated with its mRNA (≈+43 %). Finally, PA increased TET1 mRNA levels (≈+15 %) and decreased expression of DNMT3B mRNA (≈−28 %).
Our results suggest that PA-modulated DNA methylation affects several signalling pathways/biological activities involved in the cellular oxidative stress response, chromatin organization/regulation, antioxidant activity and DNA/protein binding. These changes may positively impact clinical outcomes and improve the response to cancer treatment in post-surgery BC patients.
Display omitted
•Physical activity prevents antioxidants depletion during cancer treatment.•Antioxidant gene-specific methylation is modulated by physical activity.•Antioxidant marker changes predict variable of distress symptom outcomes.
Regular physical activity is effective as prevention and treatment for different chronic conditions related to the ageing processes. In fact, a sedentary lifestyle has been linked to a worsening of ...cellular ageing biomarkers such as telomere length (TL) and/or specific epigenetic changes (e.g. DNA methylation), with increase of the propensity to aging-related diseases and premature death. Extending our previous findings, we aimed to test the hypothesis that 12 weeks of low frequency, moderate intensity, explosive-type resistance training (EMRT) may attenuate age-associated genomic changes. To this aim, TL, global DNA methylation, TRF2, Ku80, SIRT1, SIRT2 and global protein acetylation, as well as other proteins involved in apoptotic pathway (Bcl-2, Bax and Caspase-3), antioxidant response (TrxR1 and MnSOD) and oxidative damage (myeloperoxidase) were evaluated before and after EMRT in whole blood or peripheral mononuclear cells (PBMCs) of elderly subjects. Our findings confirm the potential of EMRT to induce an adaptive change in the antioxidant protein systems at systemic level and suggest a putative role of resistance training in the reduction of global DNA methylation. Moreover, we observed that EMRT counteracts the telomeres' shortening in a manner that proved to be directly correlated with the amelioration of redox homeostasis and efficacy of training regime, evaluated as improvement of both muscle's power/strength and functional parameters.
Cardiovascular diseases (CVD) can cause various conditions, including an increase in reactive oxygen species (ROS) levels that can decrease nitric oxide (NO) availability and promote ...vasoconstriction, leading to arterial hypertension. Physical exercise (PE) has been found to be protective against CVD by helping to maintain redox homeostasis through a decrease in ROS levels, achieved by increased expression of antioxidant enzymes (AOEs) and modulation of heat shock proteins (HSPs). Extracellular vesicles (EVs) circulating in the body are a major source of regulatory signals, including proteins and nucleic acids. Interestingly, the cardioprotective role of EVs released after PE has not been fully described.
The aim of this study was to investigate the role of circulating EVs, obtained through Size Exclusion Chromatography (SEC) of plasma samples from healthy young males (age: 26.95 ± 3.07; estimated maximum oxygen consumption rate (VO2max): 51.22 ± 4.85 (mL/kg/min)) at basal level (Pre_EVs) and immediately after a single bout of endurance exercise (30’ treadmill, 70% heart rate (HR) -Post_EVs). Gene ontology (GO) analysis of proteomic data from isolated EVs, revealed enrichment in proteins endowed with catalytic activity in Post_EVs, compare to Pre_EVs, with MAP2K1 being the most significantly upregulated protein. Enzymatic assays on EVs derived from Pre and Post samples showed increment in Glutathione Reductase (GR) and Catalase (CAT) activity in Post_EVs. At functional level, Post_EVs, but not Pre_EVs, enhanced the activity of antioxidant enzymes (AOEs) and reduced oxidative damage accumulation in treated human iPS-derived cardiomyocytes (hCM) at basal level and under stress conditions (Hydrogen Peroxide (H2O2) treatment), resulting in a global cardioprotective effect.
In conclusion, our data demonstrated, for the first time, that a single 30-min endurance exercise is able to alter the cargo of circulating EVs, resulting in cardioprotective effect through antioxidant activity.
SARS-CoV-2 can lead to several systemic complications, including myocardial injuries; these might be worsened by heavy physical activity. The optimal approach to cardiac risk stratification following ...SARS-CoV-2 infection in athletes for a safe return to play (RTP) still needs defining. The aim of this study was to assess the prevalence of abnormal RTP test results, according to the protocol of Italian Federation of Sport Medicine (FMSI), which was endorsed by the Italian Ministry of Health, potentially representing COVID-19-associated cardiac injuries.
This was a prospective, multicenter, observational study. All consecutive competitive athletes who underwent COVID-19 RTP testing protocol from 1 May to 31 July 2021, across 60 Italian Centers of Sports Medicine, were enrolled in the study. Athletes were tested at least 30 days after negativization of the nasopharyngeal swab (or immediately after negativization in professional athletes or Probable Olympians). A 12-lead electrocardiography at rest and during maximal incremental exercise test with continuous O
saturation monitoring and an echocardiographic examination were part of the protocol. In athletes with "moderate" disease (NHI classification), 24 h ECG monitoring (to be performed on a training day) and Magnetic Resonance Imaging (MRI) were also performed.
A total of 4143 athletes (67.8% males and 32.2% females) (53% > 18 years, 20% 18-35 years and 16% > 35 years), from more than 40 different sport disciplines, were included in the study. The mean age was 22.5 ± 13.3 years, with ages ranging from 8 to 80 years. Of these athletes, 52.3% were asymptomatic, 46.4% manifested mild symptoms, 1.1% and 0.14% had moderate or severe symptoms, respectively, while critical illness was evident in one athlete. Abnormal echocardiographic findings were detected in 80 cases (1.9%), and pericarditis in 7 cases (0.2%); all were from mildly symptomatic athletes. Arrhythmic events were recorded in 239 athletes, with 224 (5.4%) in the exercise test and 15 (0.4%) during 24 h ECG monitoring. Ventricular arrhythmias were observed in 101 (2.4%) athletes from the total population (mostly isolated or couples of premature ventricular beats): 91 in the exercise test and 10 during 24 h ECG monitoring. Cardiac magnetic resonance was performed in 34 athletes; the presence of myocarditis was confirmed in 5 athletes (0.12% of the total population, 14.7% of athletes in which MRI was performed).
According to our results, cardiac complications from SARS-CoV-2 in asymptomatic or mildly symptomatic competitive athletes are rare, and an RTP assessment based on symptoms and ECG-monitored exercise test would ensure a safe RTP in these athletes.
Hormone therapy following surgery reduces the risk of breast cancer (BC) recurrence and progression of hormone-sensitive BC, especially in postmenopausal women. Despite the antitumor efficacy of ...hormone therapy, particularly of aromatase inhibitors, they cause long-term side effects, mainly bone density reduction. Exercise can slow the rate of bone loss, which reduces the risk of fractures from osteoporosis, and could be an integrative treatment able to mitigate the BC treatment side effects positively impacting bone health. This narrative review aims to discuss studies on the effect of exercise on bone health in BC women undergoing aromatase inhibitors, highlighting the possible role of exercise as complementary to conventional therapies. Additionally, according to the literature revision, exercise practical applications to improve bone health in these patients are summarized.
•AIs increase risk of osteoporosis in Breast Cancer postmenopausal women.•Exercise is an effective complementary therapy reducing risk related to AIs therapy.•High-impact and multicomponent training are effective for osteogenic stimulation.•Exercise can positively affect bone health in BC patients undergoing AIs therapy.
PDF
