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1.
Data Brief ; 39: 107473, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34712751

RESUMEN

This dataset includes two kinds of data (for inventory analysis in Table A1 to A13, and precondition of waste and recycle for plastic and cardboard in Table A14) for conducting life cycle assessment (LCA) of strawberry-package supply chain with considering food loss during transportation Inventory analysis includes input data for LCA analysis. The data in the inventory was referenced from the publication of Plastic Waste Management Institute Plastic Waste Management Institute, (2017) and calculated based on the damage area ratio measured in our co-submitted article (Sasaki et al., 2022). This data helps to reproduce the article (Sasaki et al., 2022) for inventory analysis and re-analyze the environmental impact through the life cycle of strawberry assessed in the co-submitted article. Data of waste (incineration and landfill) and recycle ratios for plastic was collected from the previous reports of the publication Basic Knowledge of Plastic Recycle 2021 (Plastic Waste Management Institute, 2021), and data of the ratios for cardboard was referenced from Transition of Collect Rate on Cardboard (Ministry of the Environment (MOE), 2016). Ratios in this data show Japan-specialized values and is useful for creating the inventory.

2.
Can J Physiol Pharmacol ; 99(3): 278-283, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32687724

RESUMEN

The telomere length and its distribution were compared between patients administered with and without hypnotics to see if regular administration of hypnotics is associated with their aging-related somatic telomere shortening. Male patients presented significant shortening of telomere length of circulating leukocytes in association with age (-41.9 bp/year, p = 0.045) in contrast with controls (-18.3 kb/year, p = 0.155). On the other hand, female patients presented no significant shortening of telomere length with aging (-16.4 bp/year, p = 0.372) in contrast with controls (-55.9 bp/year, p = 0.00005). These results suggested that regular administration of hypnotics is associated with aging progression in a gender-related manner. The administration of hypnotics could be an indicator as the somatic aging status and for the screening of background lifestyle-associated diseases promoting biological aging.


Asunto(s)
Hipnóticos y Sedantes/farmacología , Acortamiento del Telómero/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Envejecimiento/efectos de los fármacos , Femenino , Humanos , Leucocitos/efectos de los fármacos , Leucocitos/ultraestructura , Estilo de Vida , Masculino , Persona de Mediana Edad , Caracteres Sexuales
3.
Mol Cell Biochem ; 476(1): 157-163, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32888159

RESUMEN

We explored the association of fecal bacterial species and somatic telomere changes in patients with chronic disease. The results showed that the length of the combined range of telomere and the methylated subtelomere was correlated with the increase of bacteria species and the numerical superiority of certain strains in feces, the increase of streptococci in men and women, and the increase of E. coli specifically in women. These results suggest that the aging status reflected by telomere length and/or demethylation of neighboring regions correlate with intestinal conditions which influences the proportion of the intestinal microbial population. Shortened telomere length and subtelomeric demethylation status are thought to represent the degree of aging and the accelerating stage of aging velocity, respectively. Hence, the observed biased microbial status is considered to be associated with advanced stage or acceleration phase of biological aging.


Asunto(s)
Cromosomas/ultraestructura , Microbioma Gastrointestinal , Mucosa Intestinal/microbiología , Acortamiento del Telómero , Telómero/ultraestructura , Adulto , Anciano , Envejecimiento , Bacterias/metabolismo , Metilación de ADN , Escherichia coli/metabolismo , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Persona de Mediana Edad , Análisis de Regresión
4.
Mol Cell Biochem ; 476(1): 221-229, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32918706

RESUMEN

The aims of this study were to investigate the impact of caloric restriction (CR) on cardiac senescence in an animal model of diabetes and examine the signal transduction mechanisms for changes in cell survival as well as cardiac function. Male 8-week-old Otsuka Long-Evans Tokushima fatty (OLETF) diabetic rats were divided into 2 groups: a group fed ad libitum (AL), and a group fed with CR (30% energy reduction). Long-Evans Tokushima Otsuka (LETO) non-diabetic rats were used as controls. LETO rats were divided into 3 groups: a high fat diet (HFD) group with a 22% increase in caloric intake, a CR group, and a group fed AL. At 40 weeks of age, the telomere length was significantly shorter in the heart tissue of HFD rats but was not altered by CR in experimental rats with or without CR, however, telomerase activity in both strains of CR rats was significantly elevated. Protein expression of IGF-1, Sirt 1 and phospho-FoxO1 was increased in both CR groups. Echocardiography showed that CR preserved LV diastolic function with a significantly shorter E-wave deceleration time and a greater E/A ratio compared with the AL groups. These findings suggest that CR protocol increased telomerase activity without changing of telomere length, enhanced autophagy and improved LV diastolic function in animal model of diabetes rats. It is finally suggested that those impacts may be important for the maintenance of normal cardiac function and for delayed cardiac aging.


Asunto(s)
Restricción Calórica , Diabetes Mellitus Experimental/metabolismo , Corazón , Obesidad/metabolismo , Envejecimiento , Animales , Peso Corporal , Senescencia Celular , Modelos Animales de Enfermedad , Ecocardiografía , Masculino , Ratas , Ratas Endogámicas OLETF , Telomerasa/metabolismo , Telómero/ultraestructura
5.
Can J Physiol Pharmacol ; 97(11): 1090-1093, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31340127

RESUMEN

Biological aging underlies lifestyle-related diseases. It can be assessed by measuring personal somatic cell telomere length. However, measuring the telomere length is laborious, and its clinical surrogate parameters have not been developed. This study analyzed the correlation between telomere length in peripheral leukocytes and laboratory data to select test items relating closely to biological aging. We established formulas from these clinical data to predict the personal telomere length. The subjects were patients having visited Kyushu University Beppu Hospital from 2012 to 2015. Two hundred and thirty-two patients were enrolled. The blood data were collected and telomere lengths were measured by Southern blotting method. The patients showed significant correlations between the telomere length and several blood test data with a sex-related difference. Candidate formulas are as follows: Predicted telomere length (kb) in men = 8.59 - 0.037 × Age (years) + 0.024 × Hemoglobin (g/dL); Predicted telomere length (kb) in women = 4.83 - 0.019 × Age (years) + 0.23 × Albumin (g/dL) + 0.0001 × White blood cells (/mm3) + 0.0020 × Red blood cells (× 104/mm3) + 0.0032 × Total cholesterol (mg/dL). Thus, the derived formulas allow for the accurate differential prediction of telomeric length in male and female patients.


Asunto(s)
Biometría/métodos , Análisis Químico de la Sangre , Telómero/genética , Anciano , ADN/genética , Femenino , Hemoglobinas/análisis , Humanos , Masculino
6.
Can J Physiol Pharmacol ; 97(4): 335-339, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30785764

RESUMEN

Telomere shortening is well known to be associated with the aging process and aging-associated diseases, including diabetes. The telomere length and subtelomeric methylation status in peripheral leucocytes (LTL) were compared in elderly type 2 diabetes (T2D) patients and diabetes-free controls (C). The methylation status was analyzed between MspI-TRF lengths and HpaII-TRF lengths by using methylation-sensitive and -insensitive restriction enzyme isoschizomers, MspI and HpaII, respectively. The mean telomere lengths, MspI-TRF or HpaII-TRF, were not significantly different between C and T2D patients. The percentage of fractionated densitometry showed that long and middle telomeres (>9.4 kb, 4.4-9.4 kb) were unaltered but short telomeres (<4.4 kb) in T2D patients were increased compared with C group. The methylation status revealed subtelomeric hypomethylation in short telomeres of T2D patients. When some patients with T2D were treated with 3-hydroxy-3-methylglutaril coenzyme A (HMG-CoA) reductase inhibitors (statin), results seen in short telomere of T2D patients were not observed and were not different from C. This suggested that this altered subtelomeric hypomethylation may be associated with the accelerated telomere shortening in elderly diabetic patients. These results also mean that the subtelomeric hypomethylation can also be influenced by statin treatment in T2D.


Asunto(s)
Metilación de ADN , Diabetes Mellitus Tipo 2/genética , Telómero/genética , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
7.
Mol Cell Biochem ; 455(1-2): 1-5, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30353495

RESUMEN

Somatic telomere DNA length is known to shorten with certain disease states and senescence. Furthermore, we have reported that the telomere length of a sub-healthy population also correlates with the blood data of laboratory tests. These facts suggest that patients with shorter telomere length tend to be hospitalized more easily than patients with longer telomere length. And such hospitalization tendencies can also be reflected in differences in clinical laboratory data. To address this issue, we evaluated and compared the telomere length and clinical laboratory data of outpatients and inpatients. In this study, 35 inpatients with chronic illness and 38 outpatients with one or more weeks without hospitalization experience were enrolled. Telomere length was shorter in hospitalized patients than outpatients. Inpatients and outpatients showed significant differences in some laboratory test results. Male outpatients showed higher values of fast blood sugar, HbA1c, blood urea nitrogen, creatinine, C-reactive protein, red blood cell count, and hemoglobin. Among female outpatients, the values of aspartate aminotransferase, alanine aminotransferase, albumin, creatine kinase, red blood cell count and hemoglobin were high. Of these, only albumin levels showed a positive correlation with telomere length in both sexes. Unexpectedly, all the other clinical data distinguishing outpatients and inpatients showed no significant association with telomere length. These items appeared to be related to hospital risk independently of TL. Having a shorter somatic telomere length appeared to be at a higher risk of hospitalization. This risk can be augmented by further complications such as deterioration of nutritional status and anemia. Maintaining sufficiently high nutritional status and erythropoietic potential may lead to avoidance of clinical events that require hospitalization.


Asunto(s)
Anemia/sangre , Estado Nutricional , Caracteres Sexuales , Telómero/metabolismo , Anciano , Anciano de 80 o más Años , Anemia/patología , Glucemia/metabolismo , Proteínas Sanguíneas/metabolismo , Enfermedad Crónica , Creatinina/sangre , Recuento de Eritrocitos , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Telómero/patología , Urea/sangre
8.
Int J Angiol ; 27(4): 196-201, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30410290

RESUMEN

Following heterotopic transplantation, the rat heart undergoes atrophy and exhibits delayed cardiac relaxation without any changes in contraction and systolic Ca 2+ transients. Furthermore, the sarcoplasmic reticular Ca 2+ uptake and release activities were reduced and Ca 2+ influx through L-type Ca 2+ channels was increased in the atrophied heart. Since Ca 2+ movements at sarcolemma are intimately involved in the regulation of intracellular Ca 2+ concentration, the present study was undertaken to test if sarcolemma plays any role to maintain cardiac function in the atrophied heart.The characteristics of sarcolemmal Ca 2+ pump and Na + -Ca 2+ exchange activities were examined in 8 weeks heterotopically isotransplanted rat hearts which did not support hemodynamic load and underwent atrophy. Sarcolemmal ATP (adenosine triphosphate)-dependent Ca 2+ uptake and Ca 2+ -stimulated ATPase (adenosine triphosphatase) activities were increased without any changes in Na + -K + ATPase activities in the transplanted hearts. Although no alterations in the Na + -dependent Ca 2+ uptake were evident, Na + -induced Ca 2+ release was increased in the transplanted heart sarcolemmal vesicles. The increase in Na + -induced Ca 2+ release was observed at different times of incubation as well as at 5, 20, and 40 mM Na + . The sarcolemma from transplanted hearts also showed higher contents of phosphatidic acid, sphingomyelin, and cholesterol.These results indicate that increases in the sarcolemmal, Ca 2+ transport activities in unloaded heart may provide an insight into adaptive mechanism to maintain normal contractile behavior of the atrophic heart.

9.
Geriatr Gerontol Int ; 18(9): 1415-1419, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29978589

RESUMEN

AIM: The telomere length of somatic cells is associated with systemic aging. The attrition of somatic telomere length is accelerated in pathological conditions, such as cardiovascular diseases. However, clinical parameters of cardiac function have not been well studied in this regard. The present study examined how cardiac function was affected by telomere length and the subtelomeric methylation of peripheral leukocytes. METHODS: Telomere length was assessed by Southern blotting analysis of genomic DNA extracted from peripheral leukocytes. Subtelomeric methylation was assessed by comparison between the Southern blotting results with a restriction enzyme Msp I and those with Hpa II, a methylation-sensitive isoschizomer of Msp I. RESULTS: The following parameters were associated with telomere length and/or the subtelomeric methylation status in a sex-associated manner: PR interval, the voltage of QRS complex, QRS interval, QT interval and T wave voltage in electrocardiogram; and ejection fraction, the diameter of the left ventricle at the end diastolic phase, aortic root diameter and inferior vena cava diameter in echocardiogram. CONCLUSIONS: Cardiac function correlates not only with telomere length, but also with the distribution of the telomere length and subtelomeric DNA methylation status. These imply that the loss of young cells, the accumulation of old cells and the acceleration of such changes in the cell population relate to phenotypes of cardiac aging with relative sex specificity. Furthermore, the PR interval showed a very close association with telomeric parameters in both sexes. Hence, PR is the most reliable candidate as an indicator of biological aging in both sexes. Geriatr Gerontol Int 2018; 18: 1415-1419.


Asunto(s)
Envejecimiento/genética , Enfermedades Cardiovasculares/genética , Leucocitos Mononucleares/metabolismo , Telómero/genética , Telómero/metabolismo , Anciano , Anciano de 80 o más Años , Envejecimiento/sangre , Southern Blotting , Enfermedades Cardiovasculares/fisiopatología , Senescencia Celular , Estudios de Cohortes , Metilación de ADN , Electrocardiografía/métodos , Femenino , Pruebas de Función Cardíaca , Hospitales Universitarios , Humanos , Japón , Masculino , Persona de Mediana Edad , Análisis de Regresión , Medición de Riesgo , Factores Sexuales
10.
Sci Rep ; 8(1): 133, 2018 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-29317745

RESUMEN

Although body-warming with hot spa-bathing has been proposed to exert medical therapeutic effects on certain diseases, whether body-warming has preventive and promotive effects remains unknown. To clarify this issue, an epidemiological questionnaire study regarding personal hot spa-bathing habits and disease history was carried out in Japan, where individuals engage in daily warm water bathing. Questionnaires regarding hot spa-bathing habits and disease history were randomly sent to 20,000 residents aged ≥65 years living in Beppu, a city in Japan that has the highest concentration of hot spa sources in the world. The results showed that habitual hot spa-bathing exerts preventive or promotive effects on the occurrence of certain diseases, such as hypertension (preventive) and collagen disease (promotive) in women, and cardiovascular diseases (preventive) and colon cancer survival (promotive) in men. These findings suggest that habitual body warming is an effective and economical method with beneficial preventive and promotive effects on various diseases.


Asunto(s)
Baños , Hábitos , Evaluación del Impacto en la Salud , Estilo de Vida Saludable , Factores de Edad , Anciano , Anciano de 80 o más Años , Baños/métodos , Femenino , Evaluación Geriátrica , Humanos , Japón , Masculino , Vigilancia en Salud Pública
11.
Mol Cell Biochem ; 444(1-2): 87-92, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29214470

RESUMEN

Spa bathing is known as a medical treatment for certain diseases causing chronic pains. Spa water contains mineral components which lower the specific heat of the water, resulting in a higher efficiency to warm body-core temperature. This phenomenon yields pain-relieving effect for rheumatoid arthritis, low back pain, sciatic neuralgia, fibromyalgia, etc. Here we introduce medical and biological effects of mud-spa-bathing therapy for fibromyalgia other than pain relief, the changes of blood examination data, and the telomere length of circulating leukocytes. The enrolled 7 patients with fibromyalgia syndrome were hospitalized and were subject to daily mud bathing at 40 °C for 10 min for about a month. Then, their subjective pain was reduced to about a quarter in average. They also showed lowered serum triglyceride and C-reactive protein level, maintaining the levels of aspartate transaminase and creatine phosphokinase, and increases of the red blood cell count, the serum albumin level, and the serum LDL-cholesterol level in comparison with cases without mud-bathing therapy, suggesting that mud bathing prevents inflammation and muscle atrophy and improves nutritional condition in fibromyalgia. In addition, the analysis of telomere length of peripheral leukocytes revealed a trend of negative correlation between telomere shortening and laboratory data change of hemoglobin and serum albumin. These telomeric changes can be explained hypothetically by an effect of mud bathing extending life-span of circulating leukocytes.


Asunto(s)
Envejecimiento , Fibromialgia , Peloterapia , Manejo del Dolor , Dolor , Homeostasis del Telómero , Anciano , Envejecimiento/metabolismo , Envejecimiento/patología , Femenino , Fibromialgia/metabolismo , Fibromialgia/patología , Fibromialgia/terapia , Humanos , Masculino , Persona de Mediana Edad , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Atrofia Muscular/terapia , Dolor/metabolismo , Dolor/patología
12.
J Cardiol ; 69(2): 417-427, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27374189

RESUMEN

BACKGROUND: Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme affected in heart/muscle-specific MnSOD-deficient mice (H/M-SOD2-/-), which develop progressive congestive heart failure and exhibit pathology typical of dilated cardiomyopathy. METHODS: In this study we investigated the beneficial effects of epigallocatechin gallate (EGCG) on the cardiac remodeling and telomere biology in H/M-SOD2-/- mice. H/M-SOD2-/- mice were divided into three groups: those receiving normal drinking water (KO), a low dose of EGCG (L: 10mg/L), and a high dose of EGCG (H: 100mg/L) beginning at eight weeks of age and lasting for eight weeks. RESULTS: The mice in the KO group exhibited significantly dilated cardiac remodeling with reduced contractility, which was prevented by the administration of EGCG. Although the mortality of KO mice was about 50% at 16 weeks of age, the mice that received EGCG had a high survival rate. The cardiac dilatation with reduced cardiac contraction in KO mice was prevented by EGCG treatment. The levels of myocardial oxidative stress and free fatty acids were lower in the group treated with EGCG compared with the KO group. The increased expression of nitric oxide synthase 2, nitrotyrosine, fatty acid synthase, Toll-like receptor 4, and Sirt1 in the KO mice were prevented by EGCG treatment. The shortening of the telomere length, decreased telomerase activity in KO mice were also prevented by EGCG. CONCLUSIONS: H/M-SOD2-/- mice receiving EGCG have a lower mortality rate and exhibit less inflammation and a better preserved cardiac function and telomere biology.


Asunto(s)
Antioxidantes/administración & dosificación , Catequina/análogos & derivados , Insuficiencia Cardíaca/tratamiento farmacológico , Animales , Catequina/administración & dosificación , Modelos Animales de Enfermedad , Ácido Graso Sintasas/efectos de los fármacos , Ácidos Grasos no Esterificados/metabolismo , Ratones , Ratones Noqueados , Miocardio/metabolismo , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Sirtuina 1/efectos de los fármacos , Superóxido Dismutasa/genética , Telomerasa/efectos de los fármacos , Acortamiento del Telómero/efectos de los fármacos , Receptor Toll-Like 4/efectos de los fármacos , Tirosina/análogos & derivados , Tirosina/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos
13.
Kyobu Geka ; 69(9): 778-81, 2016 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-27476568

RESUMEN

In patients with Marfan syndrome, cardiovascular complication due to aortic dissection represents the primary cause of death. Iatrogenic acute aortic dissection during cardiac surgery is a rare, but serious adverse event. A 51-year-old woman with Marfan syndrome underwent elective aortic surgery and mitral valve reconstruction surgery for the enlarged aortic root and severe mitral regurgitation. We replaced the aortic root and ascending aorta based on reimplantation technique. During subsequent mitral valve reconstruction, we found the heart pushed up from behind. Trans-esophageal echocardiography revealed a dissecting flap in the thoracic descending aorta. There was just weak signal of blood flow in the pseudolumen. We did not add any additional procedures such as an arch replacement. Cardio-pulmonary bypass was successfully discontinued. After protamine sulfate administration and blood transfusion, blood flow in the pseudolumen disappeared. The patient was successfully discharged from the hospital on 33th postoperative day without significant morbidities.


Asunto(s)
Aorta/cirugía , Insuficiencia de la Válvula Aórtica/cirugía , Síndrome de Marfan/complicaciones , Válvula Mitral/cirugía , Enfermedad Aguda , Insuficiencia de la Válvula Aórtica/complicaciones , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Procedimientos Quirúrgicos Cardíacos , Femenino , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Persona de Mediana Edad , Procedimientos de Cirugía Plástica , Reimplantación , Tomografía Computarizada por Rayos X
14.
Mol Cell Biochem ; 403(1-2): 1-11, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25662949

RESUMEN

The aims of this study were to investigate the impact of caloric restriction (CR) on cardiac telomere biology in an animal model of diabetes and to examine the signal transduction involved in cell senescence as well as cardiac function. Male 8-week-old Otsuka Long-Evans Tokushima fatty (OLETF) diabetic rats were divided into two groups: a group fed ad libitum (OLETF-AL) and a group fed with CR (OLETF-CR: 30% energy reduction). Long-Evans Tokushima Otsuka (LETO) non-diabetic rats were used as controls. LETO rats were also divided into two groups: a CR (LETO-CR) group and a group fed AL (LETO-AL). At 40 weeks of age, the body weight was decreased by 9.7% and the insulin resistance was less in OLETF-CR rats. Telomerase activity in OLETF-CR rats was significantly increased, and telomerase reverse transcriptase was more highly expressed in those rats. However, the telomere length (TL) was not different between AL- and CR-treated rats of each strain. The protein expressions for FoxO1 and FoxO3 were increased in OLETF-AL rats, but the levels of phosphorylated (p)-Akt were decreased compared to those in OLETF-CR rats. Autophagic LC3II signals revealed significant increases in OLETF-CR rats. Echocardiography showed that OLETF-CR improved the left ventricular diastolic dysfunction without changes in the left ventricular dimension. This study revealed that CR increases cardiac telomerase activity without TL attrition, and significantly ameliorates diastolic dysfunction. These findings suggest that cardiac telomerase activity may play an important role in the maintenance of normal cardiac function.


Asunto(s)
Autofagia , Restricción Calórica , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/fisiopatología , Diástole , Corazón/fisiopatología , Telomerasa/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Beclina-1 , Western Blotting , Caspasa 3/metabolismo , Diabetes Mellitus Experimental/patología , Ecocardiografía , Proteína Forkhead Box O3 , Factores de Transcripción Forkhead/metabolismo , Masculino , Proteínas Asociadas a Microtúbulos/metabolismo , Miocardio/enzimología , Miocardio/patología , Proteínas del Tejido Nervioso/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Endogámicas OLETF , Superóxido Dismutasa/metabolismo
15.
Mol Cell Biochem ; 400(1-2): 183-7, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25424527

RESUMEN

Lipid peroxidation due to oxidative stress (OS) may play an important role in the pathogenesis of chronic systemic inflammatory diseases such as multiple sclerosis (MS). Telomeres, repeated sequences that cap chromosome ends, undergo shortening with each cycle of cell division, resulting in cellular senescence. Research regarding telomere shortening has provided novel insight into the pathogenesis of various diseases. We hypothesized that OS damage leads to inflammatory reactions, which subsequently shortens the telomere length in MS. We enrolled 59 patients with MS, and age- and gender-matched 60 healthy controls. We divided MS subjects into three groups matched for age and gender according to the severity of disability: relatively benign course (BMS), secondary progressive MS, and primary progressive MS (PPMS). We analyzed the telomere length in peripheral blood mononuclear cells and the 8-iso-PGF2α concentration in urine, a reliable and stable marker of lipid peroxidation in vivo. The data showed significant higher levels of urinary 8-iso-PGF2α in MS subjects than in the controls. The lag-time, which represents the direct measurement of the resistance of low-density lipoprotein to oxidation, was shorter in the PPMS subjects than in the groups. Compared to that observed in the controls, the mean telomere length was significantly shorter in the PPMS group, whereas no significant telomere shortening was found between the controls and other subjects. Our data suggest that a decreased telomere length and enhanced lipid peroxidation reflects the severest stage of MS.


Asunto(s)
Esclerosis Múltiple/sangre , Esclerosis Múltiple/orina , Estrés Oxidativo , Acortamiento del Telómero/genética , Adulto , Dinoprost/análogos & derivados , Dinoprost/orina , Femenino , Humanos , Leucocitos Mononucleares/patología , Peroxidación de Lípido/genética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/genética
16.
Mol Cell Biochem ; 397(1-2): 305-12, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25142166

RESUMEN

The pathophysiological alterations of vascular endothelial cells induced by heat were studied. Human umbilical venous endothelial cells were cultured for 1 day at three different temperatures (37, 39, and 42 °C). The telomere lengths, the expressions of proteins associated with telomere length maintenance, apoptosis, heat shock, and vascular function were analyzed. The cell growth was not suppressed at 39 °C but suppressed at 42 °C. The mean telomere length did not change, whereas the telomere length distribution altered at 42 °C. Long telomere decreased and middle-sized telomere increased in the telomere length distribution at 42 °C. The telomerase activity did not show any heat-associated alterations. However, of the components of telomerase, telomerase reverse transcriptase was up-regulated along temperature elevation. In contrast, the expression level of RNA component TERC did not altered. Among the analyzed apoptosis-associated proteins, p21 was down-regulated and phosphorylated p53 was up-regulated. Heat shock proteins and NO synthase were up-regulated at 42 °C. These results suggested that induced growth suppression or cell senescence was induced by strong heat stress rather than mild one predominantly in cells bearing long telomeres with p53 activation, and simultaneously activated some telomere-associated factors, heat shock proteins, and NO synthesis probably for heat-resistant cell survival.


Asunto(s)
Regulación de la Expresión Génica/fisiología , Respuesta al Choque Térmico/fisiología , Calor , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Telómero/metabolismo , Supervivencia Celular/fisiología , Senescencia Celular/fisiología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Óxido Nítrico Sintasa de Tipo III/biosíntesis , ARN/biosíntesis , Telomerasa/biosíntesis , Proteína p53 Supresora de Tumor/biosíntesis
17.
Mol Cell Biochem ; 396(1-2): 129-35, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25060906

RESUMEN

Ionizing radiation (IR) is known to be a cause of telomere dysfunction in tumor cells; however, very few studies have investigated X-ray-related changes in telomere length and the telomerase activity in normal human cells, such as umbilical vein endothelial cells (HUVECs). The loss of a few hundred base pairs from a shortened telomere has been shown to be important with respect to cellular senescence, although it may not be detected according to traditional mean telomere length [assessed as the terminal restriction fragment (TRF)] analyses. In the present study, a continuous time window from irradiation was selected to examine changes in the telomere length, including the mean TRF length, percentage of the telomere length, telomerase activity, apoptotic rate, and survival rate in HUVECs from the first day to the fourth day after the administration of a 0.5-Gy dose of irradiation. The mean TRF length in the irradiated HUVECs showed shorter telomere length in first 3 days, but they were not statistically significant. On the other hand, according to the percentage analysis of the telomere length, a decreasing tendency was noted in the longer telomere lengths (9.4-4.4 kb), with a significant increase in the shortest telomeres (4.4-2.3 kb) among the irradiated cells versus the controls from the first day to the third after irradiation; no significant differences were noted on the fourth day. These results suggest that the shortest telomeres are sensitive to the late stage of radiation damage. The proliferation of irradiated cells was suppressed after IR in contrast to the non-irradiated cells. The apoptotic rate was elevated initially both in IR- and non-IR-cells, but that of IR-cells was maintained at an elevated level thereafter in contrast to that of non-IR-cells decreasing promptly. Therefore, a 0.5-Gy dose of IR induces persistent apoptosis leading to an apparent growth arrest of the normal HUVECs.


Asunto(s)
Células Endoteliales de la Vena Umbilical Humana/efectos de la radiación , Telómero/efectos de la radiación , Apoptosis/genética , Apoptosis/efectos de la radiación , Supervivencia Celular/genética , Supervivencia Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Humanos , Telomerasa/metabolismo , Proteína 1 de Unión a Repeticiones Teloméricas/metabolismo , Proteína 2 de Unión a Repeticiones Teloméricas/metabolismo , Rayos X
18.
Aging Clin Exp Res ; 25(3): 231-8, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23740586

RESUMEN

Temperature-associated alteration in the telomere lengths of vascular endothelial cells has not been well investigated. Telomere length of human umbilical vein endothelial cells (HUVECs) cultured at a high temperature (42 °C) was analyzed. Here described are heat-associated phenotypical alterations of human vascular endothelial cell under prolonged heat stress in terms of telomere length, telomerase activity, and the expression of telomere associated proteins and heat shock proteins. The genomic DNA extracted from HUVECs cultured for 3 days under 42 °C was digested with methylation-sensitive and -insensitive isoschizomers and was subjected to genomic Southern blot probed with a telomere DNA fragment. Their telomere lengths and telomere length distributions were analyzed. Telomerase activity and the expressions of telomere-associated RNA, telomere-associated proteins (TERC, TERT, TRF1, and TRF2), and heat shock proteins (Hsp60, Hsp70, and Hsp90) were also analyzed. At 42 °C, cell growth was suppressed and the cell senescence rate was transiently elevated. A proportional decrease in the number of long telomeres was observed transiently at 42 °C. A trend of subtelomeric hypomethylation and lowered telomerase activity were observed at 42 °C after 3-day culture. The altered phenotypes on day 1 seemed reactive responses for cell protection to heat, and those on day 3 seemed exhausted reactions after 3-day culture. Maintained expression was observed in Hsps, TRF2, and TERC. These altered phenotypes might contribute to cell-survival under prolonged heat stress.


Asunto(s)
Metilación de ADN/fisiología , Endotelio Vascular/patología , Calor , Homeostasis del Telómero/fisiología , Telómero/patología , Temperatura , Células Cultivadas , Senescencia Celular , Endotelio Vascular/metabolismo , Proteínas de Choque Térmico/metabolismo , Humanos , Fenotipo , ARN/metabolismo , Telomerasa/metabolismo , Telómero/fisiología , Proteína 2 de Unión a Repeticiones Teloméricas/metabolismo
19.
Aging Clin Exp Res ; 25(1): 17-23, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23740629

RESUMEN

BACKGROUNDS AND AIMS: Telomere attrition proceeds with the aging process, and is also associated with aging disease conditions, such as Alzheimer's disease (AD). The aging process also affects subtelomeric methylation status. In the present study, the telomere length and the subtelomeric methylation status in female AD patients were analyzed to see how AD affects telomere structure. METHODS: Terminal restriction fragment length of 23 AD patients' peripheral leukocytes was analyzed with methylation sensitive- and insensitive-isoschizomer by Southern blot. RESULTS: AD patients were found to have normal mean telomere lengths (controls; 6.4 ± 0.9 kb, AD; 6.1 ± 0.8 kb, p = 0.131), a proportionally decreased number of the longest telomeres (>9.4 kb) (controls; 30.3 ± 7.9%, AD; 24.4 ± 8.3%, p = 0.013), increased medium-sized telomeres (controls; 51.7 ± 3.3%, AD 55.5 ± 6.4%, p = 0.015) and unchanged numbers of the shortest telomeres (<4.4 kb) (controls; 18.0 ± 7.8, AD; 20.2 ± 8.9%, p = 0.371) in their peripheral leukocytes. The subtelomeres of telomeres in the shortest range (<4.4 kb) were more methylated in AD subjects than in controls (controls; 0.21 ± 0.23, AD; 0.41 ± 0.26, p = 0.016). CONCLUSIONS: These results may indicate that AD contributes to the loss of cells bearing the shortest telomeres, with hypomethylation of subtelomeres occurring in addition to telomere attrition, resulting in an apparent normal mean telomere length in AD patients. The relatively high subtelomeric methylation status of the shortest telomeres in peripheral blood leukocytes may be a characteristic of AD. This report demonstrates that the epigenetic status of the telomeric region is affected by disease conditions.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Metilación de ADN , Homeostasis del Telómero , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Estudios de Casos y Controles , Femenino , Humanos , Leucocitos/metabolismo , Leucocitos/patología
20.
Int J Radiat Biol ; 89(2): 106-9, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23020808

RESUMEN

PURPOSE: The telomere length of somatic cells shortens with age and with other endogenous and exogenous pathogenic factors. However, the effects of radiation therapy on telomere DNA of non-cancer tissue have not been thoroughly investigated. This study analyzed the telomere length of inpatients with cancer treated with radiation therapy to see whether the telomere lengths change in response to therapeutic radiation. MATERIALS AND METHODS: Twenty-five patients were enrolled in the study. The patients had lung cancer, prostate cancer, thyroid cancer, hepatoma, or rectal cancer. They received radiation therapy with a dose range of 15-74 Gy. The telomere lengths and telomere length distribution in peripheral leukocytes were analyzed by using a Southern blot-based method. RESULTS: The telomere length and the telomere length distribution of the peripheral leukocytes did not change after radiation therapy. However, there was a significant proportional decrease in the short telomere fraction (< 4.4 kb) per day and per Gy. CONCLUSIONS: This observation suggested that the telomere length distribution of peripheral leukocytes could be affected by radiation therapy, and that the effect of radiation tends to appear in cells with short telomeres. Radiation therapy-associated somatic telomere length change within a short range of time, about three months or shorter, can be detected by analyzing the mean telomere length and telomere length distribution.


Asunto(s)
Leucocitos/efectos de la radiación , Neoplasias/genética , Neoplasias/radioterapia , Homeostasis del Telómero/efectos de la radiación , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/radioterapia , Estudios de Casos y Controles , ADN de Neoplasias/genética , Femenino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/radioterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/radioterapia , Tolerancia a Radiación/genética , Dosificación Radioterapéutica , Neoplasias del Recto/genética , Neoplasias del Recto/radioterapia , Acortamiento del Telómero/efectos de la radiación , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/radioterapia
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