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1.
Br J Nutr ; 127(5): 641-652, 2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-33823947

RESUMO

Calorie restriction (CR) has been shown to be one of the most effective methods in alleviating the effects of ageing and age-related diseases. Although the protective effects of CR have been reported, the exact molecular mechanism still needs to be clarified. This study aims to determine differentially expressed (DE) miRNAs and altered gene pathways due to long-term chronic (CCR) and intermittent (ICR) CR in the brain of mice to understand the preventive roles of miRNAs resulting from long-term CR. Ten weeks old mice were enrolled into three different dietary groups; ad libitum, CCR or ICR, and fed until 82 weeks of age. miRNAs were analysed using GeneChip 4.1 microarray and the target of DE miRNAs was determined using miRNA target databases. Out of a total 3,163 analysed miRNAs, 55 of them were differentially expressed either by different CR protocols or by ageing. Brain samples from the CCR group had increased expression levels of mmu-miR-713 while decreasing expression levels of mmu-miR-184-3p and mmu-miR-351-5p compared to the other dietary groups. Also, current results indicated that CCR showed better preventive effects than that of ICR. Thus, CCR may perform its protective effects by modulating these specific miRNAs since they are shown to play roles in neurogenesis, chromatin and histone regulation. In conclusion, these three miRNAs could be potential targets for neurodegenerative and ageing-related diseases and may play important roles in the protective effects of CR in the brain.


Assuntos
Restrição Calórica , MicroRNAs , Envelhecimento/fisiologia , Animais , Encéfalo/metabolismo , Restrição Calórica/métodos , Camundongos , Camundongos Endogâmicos ICR , MicroRNAs/genética , MicroRNAs/metabolismo
2.
Genes Dev ; 26(6): 542-7, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-22426531

RESUMO

The COMA/CENP-H/I kinetochore complex regulates microtubule dynamics at kinetochores. The complex is also required to generate spindle checkpoint signals in both yeast and human cells under conditions where Aurora B activity is compromised. Our data explain why mammalian cells treated with Aurora inhibitors still have a functional spindle assembly checkpoint (SAC), since the checkpoint signals through CENP-H/I/N. The SAC effect from depleting the CENP-H/I/N complex cannot be explained by a weakened SAC signal, and the complex has no role in the SAC response to paclitaxel. We propose a model to explain the differential response of human cells to nocodazole and paclitaxel.


Assuntos
Proteínas Cromossômicas não Histona/fisiologia , Proteínas de Ligação a DNA/fisiologia , Pontos de Checagem da Fase M do Ciclo Celular/fisiologia , Fuso Acromático/fisiologia , Aurora Quinase B , Aurora Quinases , Proteínas de Ciclo Celular/fisiologia , Proteínas do Citoesqueleto/fisiologia , Células HeLa , Humanos , Cinetocoros/fisiologia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Nocodazol/farmacologia , Paclitaxel/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/fisiologia , Moduladores de Tubulina/farmacologia
3.
Appl Physiol Nutr Metab ; 46(8): 866-876, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33493087

RESUMO

Calorie restriction (CR) is suggested to prevent the development of mammary tumors (MTs); however, the mechanism remains to be clarified. We aimed to determine the microRNA (miRNA) profile in mice applied to 2 different CR protocols; chronic (CCR) and intermittent (ICR) and follow the MT development. In addition, the roles of miRNAs involved in adiponectin and/or leptin signaling pathways were investigated. Mice were divided into 3 groups: ad-libitum (AL), CCR, or ICR, which comprised 3 weeks of AL feeding followed by 1 week of 60% CR in a cyclic manner. Blood and tissue collection were performed at weeks 10, 17/18, 49/50 and 81/82. Long-term CCR provided better protection compared with ICR for MT development with a delay in the MT occurrence. Adiponectin expression in mammary fat pad were significantly higher in CCR group compared with AL. Using GeneChip Array, 250 of 3195 miRNAs were differentially expressed among the dietary groups. Thirteen of 250 miRNAs were related to adiponectin and/or leptin signaling genes. Results were verified by reverse transcription polymerase chain reaction. Specifically, miR-326-3p, miR-500-3p and miR-129-5p, which are related to adiponectin and/or leptin signaling, may play important roles in the preventive effects of CR in MT development and in ageing. Thus, these miRNAs might be putative biomarkers to target for diagnostic and treatment purposes. Novelty: Type of CR and micro RNA interaction is related to ageing. miR-326-3p, miR-500-3p and miR-129-5p expression levels were differentially expressed in MT development and in ageing. The genes associated with adiponectin and/or leptin signaling pathways are regulated by certain miRNAs in the protective effects of CR.


Assuntos
Adiponectina/metabolismo , Neoplasias da Mama/metabolismo , Restrição Calórica/métodos , Leptina/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BL
4.
Cureus ; 12(1): e6737, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32133259

RESUMO

Leptin, an adipocytokine, is secreted from various tissues including the liver. The roles of both leptin and leptin receptor (ObR) in numerous pathophysiological conditions including mammary tumor (MT) development have been reported. However, the roles of leptin signaling-related proteins in the liver have not been reported previously in MT development. The objective of this study was to examine the expression levels of leptin and ObR in liver tissue of a transgenic breast cancer mouse model to investigate whether the roles of leptin in MT development are systemic or local. MMTV-TGF-α transgenic female mice were fed ad-libitum from week 10 up to week 74. Protein expression levels of leptin and ObR were measured in liver tissues of 74-week-old MMTV-TGF-α mice with and without MT by western blot. Serum leptin and insulin levels were measured using a enzyme-linked immunosorbent assay. Protein expression levels of leptin and ObR were similar in mice with MT compared to the ones without MT. Serum leptin and insulin levels were also not significantly different between the two groups. These results indicate that the effects of leptin signaling in MT development might be important at a local tissue level, such as mammary fat pad, and not as important at a systemic level.

5.
J Exp Clin Med (Samsun) ; 37(4): 119-125, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33408552

RESUMO

Obesity is associated with increased risk of breast cancer. Leptin is a well-known factor involved in obesity and its serum levels are increased in breast cancer. Hyperglycemia is another significant risk factor for breast cancer. Consistently, high glucose induces proliferation and invasion of breast cancer cells and in-vivo calorie restriction reduce tumorigenesis in rodent models. The aim of this study was to investigate the effect of leptin on the viability and mode of cell death in breast cancer cells incubated in different glucose concentrations to represent caloric restriction. For this purpose, MCF-7 and T47D breast cancer cells incubated in different glucose concentrations for a total of 72 hours were treated with or without leptin either for one hour or 24 hours and the ratio of apoptotic, necrotic and alive cells were analyzed by flow cytometry. Our data revealed that glucose incubation significantly decreased apoptosis and necrosis, while increasing viability in both cell lines in a dose dependent manner. One-hour leptin treatment significantly decreased viability, and increased apoptosis but did not significantly affect necrosis in T47D cells incubated in 2.5 mM glucose. In MCF-7 cells, one-hour leptin incubation significantly increased necrosis but its effects on apoptosis and viability were not significant. In conclusion, although glucose induces cell death by apoptosis and necrosis in T47D and MCF-7 cells respectively in a dose dependent manner, the overallviability is still increased in both cell lines. One-hour leptin treatment reverses the effect of low glucose incubation on apoptosis of T47D and necrosis of MCF-7 cells. Moreover, the effect of one-hour leptin treatment on apoptosis or necrosis is significantly higher than that of 24-hour leptin treatment.

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