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Exposure to microgravity during spaceflight induces the alterations in endothelial cell function associated with post-flight cardiovascular deconditioning. PIEZO1 is a major mechanosensitive ion channel that regulates endothelial cell function. In this study, we used a two-dimensional clinostat to investigate the expression of PIEZO1 and its regulatory mechanism on human umbilical vein endothelial cells (HUVECs) under simulated microgravity. Utilizing quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, we observed that PIEZO1 expression was significantly increased in response to simulated microgravity. Moreover, we found microgravity promoted endothelial cells migration by increasing expression of PIEZO1. Proteomics analysis highlighted the importance of C-X-C chemokine receptor type 4(CXCR4) as a main target molecule of PIEZO1 in HUVECs. CXCR4 protein level was increased with simulated microgravity and decreased with PIEZO1 knock down. The mechanistic study showed that PIEZO1 enhances CXCR4 expression via Ca2+ influx. In addition, CXCR4 could promote endothelial cell migration under simulated microgravity. Taken together, these results suggest that the upregulation of PIEZO1 in response to simulated microgravity regulates endothelial cell migration due to enhancing CXCR4 expression via Ca2+ influx.
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Movimento Celular , Células Endoteliais da Veia Umbilical Humana , Canais Iônicos , Receptores CXCR4 , Simulação de Ausência de Peso , Receptores CXCR4/metabolismo , Receptores CXCR4/genética , Humanos , Canais Iônicos/metabolismo , Canais Iônicos/genética , Movimento Celular/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Cálcio/metabolismo , Células Endoteliais/metabolismo , Regulação da Expressão GênicaRESUMO
Purpose: This study assessed the moderating effect of gender on the indirect effects of positive and negative parenting styles on Internet addiction through interpersonal relationship problem. Methods: A cross-sectional survey of randomly sampled 1194 college students recruited voluntarily from three universities in China was conducted to assess the variables of positive and negative parenting styles, interpersonal relationship problem, and Internet addiction. Results: Positive parenting style, such as emotional warmth, was a protective factor for the development of Internet addiction, whereas negative parenting style, such as rejection and overprotection, was a potential risk factor for Internet addiction. Furthermore, interpersonal relationship problem completely mediated the association between positive parenting style and Internet addiction but partially mediated the relationship between negative parenting style and Internet addiction. Finally, gender moderated the indirect effect of parenting style on Internet addiction through interpersonal relationship problem. Conclusion: The correlation between positive parenting style and interpersonal relationship problem was considerably weaker among females, whereas the association between interpersonal relationship problem and Internet addiction was much stronger among females. For the prevention and intervention of Internet addiction, it is important to increase positive parenting style for males while enhancing interpersonal skills training for females. Further longitudinal studies should discuss the effects of paternal and maternal parenting styles on Internet addiction.
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Objective: Vestibular provocation is one of the main causes of flight illusions, and its occurrence is closely related to the susceptibility of motion sickness (MS). However, existing training programs have limited effect in improving the resistance to motion sickness. In this study, we investigated the effects of hypoxia acclimatization training (HAT) on the resistance to motion sickness. Methods: Healthy military college students were identified as subjects according to the criteria. MS model was induced by a rotary chair. Experimental groups included control, HAT, 3D roller training (3DRT), and combined training. Results: The Graybiel scores were decreased in the HAT group and the 3DRT group and further decreased in the combined training group in MS induced by the rotary chair. Participants had a significant increase in blood pressure after the rotary chair test and a significant increase in the heart rate during the rotary chair test, but these changes disappeared in all three training groups. Additionally, LFn was increased, HFn was decreased, and LF/HF was increased accordingly during the rotary chair test in the control group, but the changes of these three parameters were completely opposite in the three training groups during the rotary chair test. Compared with the control group, the decreasing changes in pupillary contraction velocity (PCV) and pupillary minimum diameter (PMD) of the three training groups were smaller. In particular, the binocular PCV changes were further attenuated in the combined training group. Conclusion: Our research provides a possible candidate solution for training military pilots in the resistance to motion sickness.
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Bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation and osteoblast function play critical roles in bone formation, which is a highly regulated process. Long noncoding RNAs (lncRNAs) perform diverse functions in a variety of biological processes, including BMSC osteogenic differentiation. Although several studies have reported that HOX transcript antisense RNA (HOTAIR) is involved in BMSC osteogenic differentiation, its effect on bone formation in vivo remains unclear. Here, by constructing transgenic mice with BMSC (Prx1-HOTAIR)- and osteoblast (Bglap-HOTAIR)-specific overexpression of HOTAIR, we found that Prx1-HOTAIR and Bglap-HOTAIR transgenic mice show different bone phenotypes in vivo. Specifically, Prx1-HOTAIR mice showed delayed bone formation, while Bglap-HOTAIR mice showed increased bone formation. HOTAIR inhibits BMSC osteogenic differentiation but promotes osteoblast function in vitro. Furthermore, we identified that HOTAIR is mainly located in the nucleus of BMSCs and in the cytoplasm of osteoblasts. HOTAIR displays a nucleocytoplasmic translocation pattern during BMSC osteogenic differentiation. We first identified that the RNA-binding protein human antigen R (HuR) is responsible for HOTAIR nucleocytoplasmic translocation. HOTAIR is essential for osteoblast function, and cytoplasmic HOTAIR binds to miR-214 and acts as a ceRNA to increase Atf4 protein levels and osteoblast function. Bglap-HOTAIR mice, but not Prx1-HOTAIR mice, showed alleviation of bone loss induced by unloading. This study reveals the importance of temporal and spatial regulation of HOTAIR in BMSC osteogenic differentiation and bone formation, which provides new insights into precise regulation as a target for bone loss.
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MicroRNAs , RNA Longo não Codificante , Animais , Humanos , Camundongos , Osso e Ossos/metabolismo , Diferenciação Celular/genética , Camundongos Transgênicos , MicroRNAs/genética , Osteogênese/genética , RNA Longo não Codificante/genéticaRESUMO
Objective: Night shifts have adverse cognitive outcomes that might be attenuated by daytime napping. The neurovisceral integration model suggests that resting vagally mediated heart rate variability (vmHRV) is linked with cognitive function. This study investigated the relationship between resting vmHRV and cognitive function after different nap durations in interns after shift work. Methods: A total of 105 interns were randomly allocated to one of three groups (non-nap, n = 35; 15-min nap, n = 35; 45-min nap, n = 35) to perform cognitive tests and resting vmHRV at 12:00, 15:00 and 18:00. Information processing (digit symbol substitution test; DSST), motor speed (finger tapping test; FTT), response selection (choice reaction time; CRT), and attention shifts (shifting attention test; SAT) were assessed. Resting vmHRV was assessed at baseline and during each cognitive task across groups. Results: Compared with the non-nap control, the 15-min and 45-min naps improved all outcome measures (including subjective sleepiness and cognitive performance) at 15:00, with some benefits maintained at 18:00. The 15-min nap produced significantly greater benefits on the FTT at 15:00 after napping than did the 45-min nap. Resting vmHRV was significantly correlated with DSST and SAT performance. In addition, FTT performance was the only significant predictor of DSST performance across different nap durations. Conclusion: Our results demonstrate links between daytime napping (in particular, a 15-min nap) and improved cognitive control in relation to autonomic activity after shift work in interns. These results indicated that autonomic activity when awake plays a crucial role in DSST and SAT performance and facilitated the understanding of differences in neurocognitive mechanisms underlying information processing after different nap durations.
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Privação do Sono , Tolerância ao Trabalho Programado , Humanos , Cognição , Sono/fisiologia , Vigília/fisiologia , Tolerância ao Trabalho Programado/fisiologiaRESUMO
The effect of cardiovascular dysfunction including orthostatic intolerance and disability on physical exercise is one of the health problems induced by long-term spaceflight astronauts face. As an important part of vascular structure, the vascular endothelium, uniquely sensitive to mechanical force, plays a pivotal role in coordinating vascular functions. Our study found that simulated microgravity induced PINK1-dependent mitophagy in human umbilical vein endothelial cells (HUVECs). Here, we explored the underlying mechanism of mitophagy induction. The ER stress induced by proteostasis failure in HUVECs promoted the Ca2+ transfer from ER to mitochondria, resulting in mitochondria Ca2+ overload, decreased mitochondrial membrane potential, mitochondria fission, and accumulation of Parkin and p62 in mitochondria and mitophagy under simulated microgravity. Moreover, we assumed that mitophagy played a vital role in functional changes in endothelial cells under simulated microgravity. Using mdivi-1 and PINK1 knockdown, we found that NLRP3 inflammasome activation was enhanced after mitophagy was inhibited. The NLRP3 inflammasome contributed to endothelial hyperpermeability and cellular migration by releasing IL-1ß. Thus, mitophagy inhibited cell migration ability and hyperpermeability in HUVECs exposed to clinostat-simulated microgravity. Collectively, we here clarify the mechanism of mitophagy induction by simulated microgravity in vitro and demonstrate the relationship between mitophagy and vascular endothelial functional changes including cellular migration and permeability. This study deepens the understanding of vascular functional changes under microgravity.
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BACKGROUND: Bell palsy (BP) is a simple peripheral facial paralysis. A variety of acupuncture treatments have been reported effective for the recovery of BP. However, the relative effectiveness of these acupuncture treatments is still unclear. Therefore, we plan to summarize the evidence and determine the most effective acupuncture treatment for BP. METHODS: We will search the following database, including The Cochrane Library, PubMed, Web of Science, EMBASE, China BioMedical Literature (CBM),China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang database, from their inceptions to April 30, 2020, in order to collect randomized controlled trials (RCTs) on acupuncture in the treatment of BP. We will use Stata16.0 and WinBUGS software for statistical analysis and draw surface under the cumulative ranking curve (SUCRA) graph for each outcome indicator to predict the order of curative effect of treatment measures. RESULTS: This study will compare and rank the effectiveness of different acupuncture methods in the treatment of BP, and the outcome indicators will include House-Brackmann Grading Scale, sequelae, Facial Disability Index score, Sunnybrook facial grading system, Portmann score, and adverse events. CONCLUSION: Our study will provide supports for clinical practice.INPLASY registration number: INPLASY202040019.
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Terapia por Acupuntura/métodos , Paralisia de Bell/terapia , Terapia por Acupuntura/efeitos adversos , Teorema de Bayes , Avaliação da Deficiência , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Projetos de Pesquisa , Índice de Gravidade de Doença , Metanálise como AssuntoRESUMO
Weightlessness-induced cardiovascular dysfunction can lead to physiological and pathological consequences. It has been shown that spaceflight or simulated microgravity can alter expression profiles of some microRNAs (miRNAs). Here, we attempt to identify the role of miRNAs in human umbilical vein endothelial cells (HUVECs) apoptosis under simulated microgravity. RNA-sequencing and quantitative real-time PCR (qRT-PCR) assays were used to identify differentially expressed miRNAs in HUVECs under simulated microgravity. Then we obtained the target genes of these miRNAs through target analysis software. Moreover, GO and KEGG enrichment analysis were performed. The effects of these miRNAs on HUVECs apoptosis were evaluated by flow cytometry, Western blot and Hoechst staining. Furthermore, we obtained the target gene of miR-27b-5p by luciferase assay, qRT-PCR and Western blot. Finally, we investigated the relationship between this target gene and miR-27b-5p in HUVECs apoptosis under normal gravity or simulated microgravity. We found 29 differentially expressed miRNAs in HUVECs under simulated microgravity. Of them, the expressions of 3 miRNAs were validated by qRT-PCR. We demonstrated that miR-27b-5p affected HUVECs apoptosis by inhibiting zinc fingers and homeoboxes 1 (ZHX1). Our results reported here demonstrate for the first time that simulated microgravity can alter the expression of some miRNAs in HUVECs and miR-27b-5p may protect HUVECs from apoptosis under simulated microgravity by targeting ZHX1.
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Apoptose , Células Endoteliais da Veia Umbilical Humana/citologia , Ausência de Peso/efeitos adversos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Células Endoteliais da Veia Umbilical Humana/química , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Astronauts exposed to a gravity-free environment experience cardiovascular deconditioning that causes post-spaceflight orthostatic intolerance and other pathological conditions. Endothelial dysfunction is an important factor responsible for this alteration. Our previous study showed enhanced autophagy in endothelial cells under simulated microgravity. The present study explored the cytoprotective role of autophagy under microgravity in human umbilical vein endothelial cells (HUVECs). We found that clinorotation for 48 h induced apoptosis and endoplasmic reticulum (ER) stress in HUVECs. ER stress and the unfolded protein response (UPR) partially contributed to apoptosis under clinorotation. Autophagy partially reduced ER stress and restored UPR signaling by autophagic clearance of ubiquitin-protein aggregates, thereby reducing apoptosis. In addition, the ER stress antagonist 4-phenylbutyric acid upregulated autophagy in HUVECs. Taken together, these findings indicate that autophagy plays a protective role against apoptosis under clinorotation by clearing protein aggregates and partially restoring the UPR.
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Apoptose , Gravidade Alterada/efeitos adversos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Fenilbutiratos/farmacologia , Autofagia/efeitos dos fármacos , Linhagem Celular , Estresse do Retículo Endoplasmático , Humanos , Substâncias Protetoras/farmacologia , Rotação/efeitos adversos , Resposta a Proteínas não DobradasRESUMO
Individuals exposed to long-term spaceflight often experience cardiovascular dysfunctions characterized by orthostatic intolerance, disability on physical exercise, and even frank syncope. Recent studies have showed that the alterations of cardiovascular system are closely related to the functional changes of endothelial cells. We have shown previously that autophagy can be induced by simulated microgravity in human umbilical vein endothelial cells (HUVECs). However, the mechanism of enhanced autophagy induced by simulated microgravity and its role in the regulation of endothelial function still remain unclear. We report here that 48 h clinorotation promoted cell migration in HUVECs by induction of autophagy. Furthermore, clinorotation enhanced autophagy by the mechanism of human murine double minute 2 (HDM2)-dependent degradation of cytoplasmic p53 at 26S proteasome, which results in the suppression of mechanistic target of rapamycin (mTOR), but not via activation of AMPK in HUVECs. These results support the key role of HDM2-p53 in direct downregulation of mTOR, but not through AMPK in microgravity-induced autophagy in HUVECs.
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Autofagia , Movimento Celular , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Rotação , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Ácidos Graxos Insaturados/farmacologia , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana/ultraestrutura , Humanos , Leupeptinas/farmacologia , Modelos Biológicos , Fosforilação/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Tempo , Simulação de Ausência de PesoRESUMO
Numerous countermeasures have been proposed to minimize microgravity-induced physical deconditioning, but their benefits are limited. The present study aimed to investigate whether personalized aerobic exercise based on artificial gravity (AG) mitigates multisystem physical deconditioning. Fourteen men were assigned to the control group (n=6) and the countermeasure group (CM, n=8). Subjects in the CM group were exposed to AG (2 Gz at foot level) for 30 min twice daily, during which time cycling exercise of 80-95 % anaerobic threshold (AT) intensity was undertaken. Orthostatic tolerance (OT), exercise tests, and blood assays were determined before and after 4 days head-down bed rest (HDBR). Cardiac systolic function was measured every day. After HDBR, OT decreased to 50.9 % and 77.5 % of pre-HDBR values in control and CM groups, respectively. Exercise endurance, maximal oxygen consumption, and AT decreased to 96.5 %, 91.5 % and 91.8 % of pre-HDBR values, respectively, in the control group. Nevertheless, there were slight changes in the CM group. HDBR increased heart rate, sympathetic activity, and the pre-ejection period, but decreased plasma volume, parasympathetic activity and left-ventricular ejection time in the control group, whereas these effects were eliminated in the CM group. Aldosterone had no change in the control group but increased significantly in the CM group. Our study shows that 80-95 % AT aerobic exercise based on 2 Gz of AG preserves OT and exercise endurance, and affects body fluid regulation during short-term HDBR. The underlying mechanisms might involve maintained cardiac systolic function, preserved plasma volume, and improved sympathetic responses to orthostatic stress.
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Repouso em Cama/métodos , Pressão Sanguínea/fisiologia , Exercício Físico/fisiologia , Gravidade Alterada , Decúbito Inclinado com Rebaixamento da Cabeça/fisiologia , Frequência Cardíaca/fisiologia , Adulto , Humanos , Masculino , Intolerância Ortostática/diagnóstico , Intolerância Ortostática/fisiopatologia , Consumo de Oxigênio/fisiologia , Fatores de Tempo , Simulação de Ausência de Peso/métodos , Adulto JovemRESUMO
BACKGROUND/AIMS: Microgravity leads to hydrodynamic alterations in the cardiovascular system and is associated with increased angiogenesis, an important aspect of endothelial cell behavior to initiate new vessel growth. Given the critical role of Rho GTPase-dependent cytoskeleton rearrangement in cell migration, small GTPase RhoA might play a potential role in microgravity-induced angiogenesis. METHODS: We examined the organization of actin filaments by FITC-conjugated phalloidin staining, as well as the expression and activity of RhoA by quantitative PCR and Western blot, in human umbilical vein endothelial cells (HUVECs) under normal gravity and simulated microgravity. Effect of simulated microgravity on the wound closure and tube formation in HUVECs, and their dependence on RhoA, were also analyzed by cell migration and tube formation assays. RESULTS: We show that in HUVECs actin filaments are disorganized and RhoA activity is reduced by simulated microgravity. Blocking RhoA activity either by C3 transferase Rho inhibitor or siRNA knockdown mimicked the effect of simulated microgravity on inducing actin filament disassembly, followed by enhanced wound closure and tube formation in HUVECs, which closely resembled effects seen on microgravity-treated cells. In contrast, overexpressing RhoA in microgravity-treated HUVECs restored the actin filaments, and decreased wound closure and tube formation abilities. CONCLUSION: These results suggest that RhoA inactivation is involved in the actin rearrangement-associated angiogenic responses in HUVECs during simulated microgravity.
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Citoesqueleto de Actina/fisiologia , Actinas/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Neovascularização Fisiológica/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismo , Movimento Celular , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Microscopia de Fluorescência , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Simulação de Ausência de Peso , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores , Proteína rhoA de Ligação ao GTP/genéticaRESUMO
BACKGROUND/AIMS: The potential role of caveolin-1 in modulating angiogenesis in microgravity environment is unexplored. METHODS: Using simulated microgravity by clinostat, we measured the expressions and interactions of caveolin-1 and eNOS in human umbilical vein endothelial cells. RESULTS: We found that decreased caveolin-1 expression is associated with increased expression and phosphorylation levels of eNOS in endothelial cells stimulated by microgravity, which causes a dissociation of eNOS from caveolin-1 complexes. As a result, microgravity induces cell migration and tube formation in endothelial cell in vitro that depends on the regulations of caveolin-1. CONCLUSION: Our study provides insight for the important endothelial functions in altered gravitational environments.
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Cavéolas/metabolismo , Caveolina 1/metabolismo , Neovascularização Fisiológica , Óxido Nítrico Sintase Tipo III/metabolismo , Simulação de Ausência de Peso , Caveolina 1/análise , Movimento Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Óxido Nítrico Sintase Tipo III/análise , Mapas de Interação de ProteínasRESUMO
OBJECTIVE: Spaceflight is associated with cardiovascular deregulation. However, the influence of microgravity on the cardiovascular system and its mechanisms and countermeasures remain unknown. Our previous studies have demonstrated that transcutaneous electrical acupuncture stimulation (TEAS) is effective in improving orthostatic tolerance (OT). The purpose of this study was to determine if TEAS treatment can attenuate cardiovascular deconditioning induced by a 4-day -6° head-down bed rest (HDBR). METHODS: Fourteen healthy male subjects were randomly allocated to a control group (control, n=6, 4â days HDBR without countermeasures) and a TEAS treatment group (TEAS, n=8, 4â days HDBR with TEAS at Neiguan (PC6) for 30â min each day for 4 consecutive days during HDBR). OT, plasma hormones, plasma volume and heart rate variability were assessed before and after HDBR. Cardiac function and cerebral blood flow were measured before, during and after HDBR. RESULTS: The data showed that TEAS treatment mitigated the decrease in OT that was observed in the control group and cardiac function, alleviated autonomic dysfunction, and partially prevented plasma volume reduction after HDBR. Angiotensin II and aldosterone were significantly increased by 129.3% and 133.3% after HDBR in the TEAS group (p<0.05). CONCLUSIONS: These results indicate that 30â min of daily TEAS treatment at PC6 is partially effective in maintaining OT, probably due to increased plasma volume-regulating hormones and activation of the peripheral sympathetic nervous system. TEAS treatment appears effective at reducing cardiovascular deconditioning induced by HDBR for 4â days. TRIAL REGISTRATION NUMBER: NCT02300207.
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Repouso em Cama , Descondicionamento Cardiovascular , Eletroacupuntura , Decúbito Inclinado com Rebaixamento da Cabeça , Adulto , Pressão Sanguínea , Circulação Cerebrovascular , Frequência Cardíaca , Hormônios/sangue , Humanos , Masculino , Intolerância Ortostática , Adulto JovemRESUMO
Data from human and rodent studies have demonstrated that microgravity induces observed bone loss in real spaceflight or simulated experiments. The decrease of bone formation and block of maturation may play important roles in bone loss induced by microgravity. The aim of this study was to investigate the changes of proliferation and differentiation in bone marrow mesenchymal stem cells (BMSCs) induced by simulated microgravity and the mechanisms underlying it. We report here that clinorotation, a simulated model of microgravity, decreased proliferation and differentiation in BMSCs after exposure to 48 h simulated microgravity. The inhibited proliferation are related with blocking the cell cycle in G2/M and enhancing the apoptosis. While alterations of the osteoblast differentiation due to the decreased SATB2 expression induced by simulated microgravity in BMSCs.
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Células da Medula Óssea/citologia , Diferenciação Celular , Proliferação de Células , Células-Tronco Mesenquimais/citologia , Animais , Sequência de Bases , Ciclo Celular , Linhagem Celular , Primers do DNA , Camundongos , Camundongos Endogâmicos C3H , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ausência de PesoRESUMO
Exposure to high sustained positive acceleration (+Gz) is known to have a pathophysiological effect on the heart of the rat. As critical regulators of cardiac myocyte survival and death, mitochondria may be crucially involved in +Gz-induced pathogenesis. It was, therefore, of interest to investigate myocardial mitochondrial ultrastructure, respiratory function, and antioxidant capacity in rats after exposure to +10 Gz for 5 min. The results showed that high +Gz stress could damage mitochondrial ultrastructure; this was apparent from swollen, degenerated, and reduced mitochondria, and mitochondrial cristae broken or disappeared. This resulted in significant changes of quantitative indicators of mitochondria morphometry, for example increased surface density, volume density, average volume, and average surface area, and reduced numerical density. The studies also revealed that exposure to +Gz stress induced dysfunction of the mitochondrial respiratory chain, reduced the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase), and increased malondialdehyde content. We thus conclude that high +Gz stress not only damaged mitochondrial ultrastructure but also impaired respiratory function and antioxidant capacity.
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Aceleração/efeitos adversos , Mitocôndrias Cardíacas/fisiologia , Mitocôndrias Cardíacas/ultraestrutura , Consumo de Oxigênio/fisiologia , Estresse Fisiológico/fisiologia , Animais , Antioxidantes/metabolismo , Centrifugação/efeitos adversos , Masculino , Malondialdeído/metabolismo , Dilatação Mitocondrial , Ratos , Ratos Sprague-DawleyRESUMO
Individuals exposed to extended periods of spaceflight or prolonged 6° head-down-tilt bed rest often suffer from health hazards represented by cardiovascular deconditioning. Many studies have reported that alterations in vascular endothelial cells contribute to cardiovascular dysfunction induced by microgravity. Autophagy, a lysosomal degradation pathway, serves an adaptive role for survival, differentiation, and development in cellular homeostasis, and can be triggered by various environmental stimuli. However, whether autophagy can be induced in endothelial cells by real or simulated microgravity remains to be determined. This study was designed to investigate the effects of simulated microgravity on the activation of autophagy in human umbilical vein endothelial cells (HUVECs). We report here that clinorotation, a simulated model of microgravity, enhances autophagosome formation, increases LC3 and beclin-1 expression, and promotes the conversion of LC3-I to LC3-II in HUVECs. These results demonstrate that simulated microgravity for 48 h activates autophagy of vascular endothelial cells.
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Autofagia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Rotação/efeitos adversos , Ausência de Peso/efeitos adversos , Proteínas Reguladoras de Apoptose/biossíntese , Proteína Beclina-1 , Descondicionamento Cardiovascular/fisiologia , Linhagem Celular , Humanos , Proteínas de Membrana/biossíntese , Proteínas Associadas aos Microtúbulos/biossíntese , Proteínas Associadas aos Microtúbulos/metabolismo , Voo EspacialRESUMO
There is evidence to suggest that microgravity/weightlessness can induce changes in lung physiology/function. We hypothesized that microgravity, induced by head-down bed rest (HDBR), would induce changes in lung function and that exercise training with artificial gravity (AG) would prevent these changes from occurring. Twelve participants were randomly assigned to a control or AG exercise countermeasure (CM) group (n = 6 per group) and 96 h of 6° HDBR. Participants in the CM group were exposed to AG (alternating 2 min intervals of +1·0 and +2·0 G) for 30 min, twice daily, during which time ergometric exercise (40 W intensity) was performed. Pulse rate, oxygen saturation (SO(2) ) and lung function were measured and compared between groups. The CM and control groups were similar in mean age, height and weight. There were no significant within or between group differences over time in pulse rate, SO(2) , vital capacity, inspiratory capacity, tidal volume, expiratory reserve volume, inspiratory reserve volume, minute ventilation, forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, maximal expiratory flow in 25%, 50% and 75% vital capacity, forced inspiratory vital capacity, forced inspiratory volume in 1 s and maximal voluntary ventilation. Microgravity induced by 96 h of HDBR does not appear to affect lung function in humans. Further, AG with exercise training does not change lung function during 96 h of HDBR in humans.
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Repouso em Cama , Exercício Físico , Gravidade Alterada , Decúbito Inclinado com Rebaixamento da Cabeça , Pulmão/fisiologia , Ventilação Pulmonar , Respiração , Simulação de Ausência de Peso , Adaptação Fisiológica , China , Humanos , Masculino , Análise Multivariada , Testes de Função Respiratória , Fatores de Tempo , Adulto JovemRESUMO
AIMS: Orthostatic intolerance (OI) is a common clinical problem; however, effective and applicable clinical prevention/treatment is limited. The aim of this study was to investigate whether electroacupuncture (EA) is a novel effective treatment in attenuating OI in healthy individuals. METHODS AND RESULTS: This study used a randomized, controlled, crossover design using two protocols. Orthostatic intolerance was induced with a combination of head-up tilt (HUT) and lower body negative pressure (LBNP). Twenty healthy individuals in Protocol 1 and 10 healthy individuals in Protocol 2 received no EA, EA at PC-6 acupuncture points (acupoint), and EA at a non-acupoint in a random order with an interim of 1 week. Electroacupuncture was administered prior to HUT/LBNP in Protocol 1 and simultaneously during HUT/LBNP in Protocol 2. Electroacupuncture at PC-6 administered either before or during HUT/LBNP postponed the occurrence of pre-syncopal symptoms, improved haemodynamic responses to HUT/LBNP (including increased diastolic blood pressure, stroke volume, and total peripheral resistance and a decreased heart rate), blunted decreases of maximum velocity and velocity time integral of blood flow in the middle cerebral artery, and increased plasma noradrenalin and adrenalin concentrations. In addition, heart rate variability analysis revealed that EA at PC-6 either before or during HUT/LBNP decreased high-frequency ranges of R-R interval while increasing low-frequency ranges of R-R interval, which indicates an elevated heart sympathetic tone. CONCLUSION: Electroacupuncture at PC-6 is effective in improving orthostatic tolerance. Cardiac function improvement and sympathetic activation are responsible for the improved orthostatic tolerance after EA. EA represents a novel intervention against OI.
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Eletroacupuntura/métodos , Intolerância Ortostática/fisiopatologia , Intolerância Ortostática/reabilitação , Sistema Nervoso Simpático/fisiopatologia , Disfunção Ventricular Esquerda/prevenção & controle , Disfunção Ventricular Esquerda/fisiopatologia , Feminino , Humanos , Masculino , Intolerância Ortostática/complicações , Valores de Referência , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia , Adulto JovemRESUMO
Endothelial cells are very sensitive to microgravity and the morphological and functional changes in endothelial cells are believed to be at the basis of weightlessness-induced cardiovascular deconditioning. It has been shown that the proliferation, migration, and morphological differentiation of endothelial cells play critical roles in angiogenesis. However, the influence of microgravity on the ability of endothelial cells to foster angiogenesis remains to be explored in detail. In the present study, we used a clinostat to simulate microgravity, and we observed tube formation, migration, and expression of endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVEC-C). Specific inhibitors of eNOS and phosphoinositide 3-kinase (PI3K) were added to the culture medium and gravity-induced changes in the pathways that mediate angiogenesis were investigated. After 24 h of exposure to simulated microgravity, HUVEC-C tube formation and migration were significantly promoted.This was reversed by co-incubation with the specific inhibitor of N-nitro-L-arginine methyl ester hydrochloride (eNOS). Immunofluorescence assay, RT-PCR, and Western blot analysis demonstrated that eNOS expression in the HUVEC-C was significantly elevated after simulated microgravity exhibition. Ultrastructure observation via transmission electron microscope showed the number of caveolae organelles in the membrane of HUVEC-C to be significantly reduced. This was correlated with enhanced eNOS activity. Western blot analysis then showed that phosphorylation of eNOS and serine/threonine kinase (Akt) were both up-regulated after exposure to simulated microgravity. However, the specific inhibitor of PI3K not only significantly downregulated the expression of phosphorylated Akt, but also downregulated the phosphorylation of eNOS. This suggested that the PI3K-Akt signal pathway might participate in modulating the activity of eNOS. In conclusion, the present study indicates that 24 h of exposure to simulated microgravity promote angiogenesis among HUVEC-C and that this process is mediated through the PI3K-Akt-eNOS signal pathway.