SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington’s Disease Mice

Tulino, Raffaella; Benjamin, Agnesska C.; Jolinon, Nelly; Smith, Donna; Chini, Eduardo N.; Carnemolla, Alisia; Bates, Gillian P.

doi:10.1371/journal.pone.0145425

Cited by 35 publications

(36 citation statements)

References 50 publications

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“…SIRT1 is a member of the Sirtuin protein family, which is associated with cell stress reaction regulation, DNA repair, chromatin recombination, metabolism, aging and apoptosis due to the acetyl enzyme function of co-enzyme NAD + to SIRT1 ( 23 , 24 ). The function of SIRT1 in cancer is unclear.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-34a regulates proliferation and apoptosis of gastric cancer cells by targeting silent information regulator 1

Deng

Zheng

et al. 2018

Exp Ther Med

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The present study aimed to identify whether microRNA (miRNA/miR)-34a regulates the proliferation and apoptosis of gastric cancer cells by targeting silent information regulator 1 (SIRT1). The expression of miR-34a and SIRT1 and cell viability was investigated in gastric cancer cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to determine miR-34a expression in gastric adenocarcinoma, normal pericarcinomatous tissues, human normal gastric mucosa epithelial cell line GES and various gastric cancer cell strains. A bioinformatics method was then used to predict the target gene of miR-34a. A human miR-34a over expression lentiviral vector system was constructed and then used for transfection of the gastric cancer cell line SCG-7901 to determine the expression of SIRT1 mRNA and SIRT1 protein using RT-qPCR and western blot analysis. The MTT method and flow cytometry was used to measure cell proliferation and apoptosis. The relative expression of miR-34a in gastric cancer tissues was significantly decreased compared with that in normal tissues (P<0.01). miR-34a expression was also significantly decreased in low differentiated N2, N3 gastric cancer tissues (P<0.01). However, tumor size and filtration degree were not significantly associated with miR-34a expression. The relative expression of miR-34a was decreased in gastric cancer cells, especially in the SGC-7901 cell line (P<0.01) compared with the GES group. The relative expression of SIRT1 protein was decreased in the miR-34a group compared with the negative control (P<0.01). The rate of proliferation was significantly decreased, whereas the rate of apoptosis was significantly increased in the miR-34a group compared with the NC group (P<0.01). Therefore, the present results suggested that miRNA-34a serves a pivotal role in gastric cancer as a cancer suppressor gene by targeting SIRT1 to regulate the proliferation and apoptosis of gastric cancer cells.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-34a regulates proliferation and apoptosis of gastric cancer cells by targeting silent information regulator 1

Deng

Zheng

et al. 2018

Exp Ther Med

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“…Hence, exogenous NAM could have beneficial effects, but this has yet to be reported. It has been noted that sirtuins, especially SIRT1, can directly influence brain function (Barhwal et al 2015;Fujitsuka et al 2016;Koltai et al 2011;Sarga et al 2013;Torma et al 2014;Tulino et al 2016). SIRT1 appears to be involved in neuronal stem cell differentiation (Ma et al 2014), synaptic plasticity (Michan et al 2010) and metabolism (Li et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Exogenous nicotinamide supplementation and moderate physical exercise can attenuate the aging process in skeletal muscle of rats

et al. 2017

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Nicotinamide (NAM) could enhance the availability of NAD ? and be beneficial to cell function. However, NAM can inhibit the activities of SIRT1 and PARP. The effect of NAM supplementation on the aging process is not well known. In the present study exogenous NAM (1-0.5% in drinking water) was supplemented for 5 weeks and in the last 4 weeks moderate treadmill running was given to 5 mo and 28 mo old rats. The content of SIRT1 was not effected by NAM treatment alone. However, the activity of SIRT1, judged from the acetylated p53/p53 ratio, increased in both NAM treated age groups, suggesting beneficial effects of exogenous NAM. This was confirmed by the finding of increased PGC-1a and pCREB/CREB ratio in the gastrocnemius muscle of old but not young NAM treated animals. Our data suggest NAM administration can attenuate the aging process in skeletal muscle of rats, but NAM administration together with exercise training might be too great challenge to cope with in the old animals, since it leads to decreased levels of SIRT1.

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“…In addition to the assessment of the presence of transgene on Sirt mRNA expression changes in key structures (striatum, overlying cortex, cerebellum) of the regulation of motor functions, our study design involved the determination of the effect of aging and its interaction with the presence of the transgene with a view on gender-related effects as well. First of all, we found no significant differences between genders regarding either of the above-mentioned aspects, and therefore gender issues seemingly did not introduce bias into the studies of Tulino et al and Reynolds et al [45,61]. Similarly to the study of Tulino et al [61], we found no effect of the transgene in the striatum regarding either age groups, but a marked increase in Sirt1 expression was demonstrated in cortical and cerebellar samples of tg animals compared to wt controls in all age groups similar to that found by Reynolds et al [45] applying whole brain samples.…”

Section: Discussionmentioning

confidence: 51%

“…Accordingly, we aimed at contributing to the clarification of the controversies regarding Sirt1 and Sirt3 mRNA expression patterns by a better characterization of region-and aging-specific changes in the mRNA expression levels of Sirt1 and three Sirt3 isoforms using the N171-82Q tg mouse model of HD. Tulino et al found a significant decrease in striatal Sirt1 mRNA expression from 4 to 9 weeks in the wt group, whereas cerebellar Sirt1 mRNA expression increased significantly by 9 and 14 weeks of age in the same control group in experiments with R6/2 mouse model of HD (MRN: 204) [61]. The presence of the transgene seemingly did not affect Sirt1 mRNA expression.…”

Section: Discussionmentioning

confidence: 97%

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Cerebellar Predominant Increase in mRNA Expression Levels of Sirt1 and Sirt3 Isoforms in a Transgenic Mouse Model of Huntington’s Disease

et al. 2020

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The potential role of Sirt1 and Sirt2 subtypes of Sirtuins (class III NAD +-dependent deacetylases) in the pathogenesis of Huntington's disease (HD) has been extensively studied yielding some controversial results. However, data regarding the involvement of Sirt3 and their variants in HD are considerably limited. The aim of this study was to assess the expression pattern of Sirt1 and three Sirt3 mRNA isoforms (Sirt3-M1/2/3) in the striatum, cortex and cerebellum in respect of the effect of gender, age and the presence of the transgene using the N171-82Q transgenic mouse model of HD. Striatal, cortical and cerebellar Sirt1-Fl and Sirt3-M1/2/3 mRNA levels were measured in 8, 12 and 16 weeks old N171-82Q transgenic mice and in their wild-type littermates. Regarding the striatum and cortex, the presence of the transgene resulted in a significant increase in Sirt3-M3 and Sirt1 mRNA levels, respectively, whereas in case of the cerebellum the transgene resulted in increased expression of all the assessed subtypes and isoforms. Aging exerted minor influence on Sirt mRNA expression levels, both in transgene carriers and in their wild-type littermates, and there was no interaction between the presence of the transgene and aging. Furthermore, there was no difference between genders. The unequivocal cerebellar Sirtuin activation with presumed compensatory role suggests that the cerebellum might be another key player in HD in addition to the most severely affected striatum. The mitochondrially acting Sirt3 may serve as an interesting novel therapeutic target in this deleterious condition.

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SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington’s Disease Mice

Cited by 35 publications

References 50 publications

MicroRNA-34a regulates proliferation and apoptosis of gastric cancer cells by targeting silent information regulator 1

MicroRNA-34a regulates proliferation and apoptosis of gastric cancer cells by targeting silent information regulator 1

Exogenous nicotinamide supplementation and moderate physical exercise can attenuate the aging process in skeletal muscle of rats

Cerebellar Predominant Increase in mRNA Expression Levels of Sirt1 and Sirt3 Isoforms in a Transgenic Mouse Model of Huntington’s Disease

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