scholarly journals Riboflavin transporter SLC52A1, a target of p53, suppresses cellular senescence by activating mitochondrial complex II

2021 ◽  
pp. mbc.E21-05-0262
Author(s):  
Taiki Nagano ◽  
Yuto Awai ◽  
Shione Kuwaba ◽  
Taiichi Osumi ◽  
Kentaro Mio ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cellular Senescence ◽  
Chain Complex ◽  
Feedback Mechanism ◽  
Complex Ii ◽  
Negative Feedback Mechanism ◽  
Transport Chain ◽  
The Relationship ◽  
Riboflavin Transport

Cellular senescence is a state of permanent proliferative arrest induced by a variety of stresses, such as DNA damage. The transcriptional activity of p53 has been known to be essential for senescence induction. It remains unknown, however, whether among the downstream genes of p53, there is a gene that has anti-senescence function. Our recent studies have indicated that the expression of SLC52A1 (also known as GPR172B/RFVT1), a riboflavin transporter, is upregulated specifically in senescent cells depending on p53, but the relationship between senescence and SLC52A1 or riboflavin has not been described. Here, we examined the role of SLC52A1 in senescence. We found that knockdown of SLC52A1 promoted senescence phenotypes induced by DNA damage in tumor and normal cells. The senescence suppressive-action of SLC52A1 was dependent on its riboflavin transport activity. Furthermore, elevation of intracellular riboflavin led to activation of mitochondrial membrane potential (MMP) mediated by the mitochondrial electron transport chain complex II. Finally, the SLC52A1-dependent activation of MMP inhibited the AMPK-p53 pathway, a central mediator of mitochondria dysfunction-related senescence. These results suggest that SLC52A1 contributes to suppress senescence through the uptake of riboflavin and acts downstream of p53 as a negative feedback mechanism to limit aberrant senescence induction.

Prospects for the use of collagen-containing matrices in directed tissue regeneration. Literature review

2021 ◽  
pp. 9-13
Author(s):  
Е. М. Boyko ◽  
A. A. Dolgalev ◽  
D. V. Stomatov ◽  
S. G. Ivashkevih ◽  
A. A. Chagarov ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Connective Tissue ◽  
Tissue Regeneration ◽  
San Antonio ◽  
Feedback Mechanism ◽  
Tissue Growth ◽  
Negative Feedback Mechanism ◽  
Decay Products ◽  
The Relationship

Studies of recent decades have convincingly shown that collagen in connective tissue plays not only a structural role. In the 80s of the XX centu[1]ry, A. Pishinger and H. Heine suggested the informative-regulatory role of collagen in the extracellular matrix (A. Pischinger, 1990). In recent years, the morphogenetic function of collagen has been actively studied, the implementation of which is possible due to the presence of collagen re[1]ceptors on the surface of various cell populations, such as platelets and fibroblasts. Collagen regulates the remodeling of the extracellular matrix (J. D. San Antonio et al., 2020). At the same time, its decay products, which stimulate growth by the negative feedback mechanism, are probably of great importance. In general, the relationship between the synthesis and breakdown of collagen is of fundamental importance for the regulation of connective tissue growth.

scholarly journals Synthesis, activation and deactivation of glucocorticoids. The biological role of cortisol in metabolic disorders

2017 ◽  
Vol 14 (2) ◽  
pp. 48-52
Author(s):  
Ekaterina V. Artemova
Keyword(s):  
Scientific Basis ◽  
Feedback Mechanism ◽  
Negative Feedback Mechanism ◽  
Target Organs ◽  
Number Of Patients ◽  
Patients With Diabetes ◽  
The Relationship ◽  
Disease Understanding

In the light of the emerging new data, the view of the hypothalamic-pituitary-adrenal-target organs system undergoes significant changes, and along with the negative feedback mechanism, there are suggestions of the existence of other regulatory mechanisms for synthesis, activation, and deactivation of glucocorticosteroids (GCS). However, there is currently a relatively small amount of data on the relationship between systemic and local cortisol production in tissues. The inconsistent increase in the number of patients with diabetes mellitus (predominantly type 2) and obesity poses new challenges in developing effective medicines and their delivery forms, Methods of timely detection and prevention of the development of the disease. Understanding these processes will create the necessary scientific basis for the search and development of new targets for the pharmacotherapy of diseases associated with a violation of synthesis, activation and action of GCS.

scholarly journals Role of histone deacetylase 2 in epigenetics and cellular senescence: implications in lung inflammaging and COPD

2012 ◽  
Vol 303 (7) ◽  
pp. L557-L566 ◽  
Author(s):  
Hongwei Yao ◽  
Irfan Rahman
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Histone Deacetylase ◽  
Dna Damage Response ◽  
Cellular Senescence ◽  
Premature Aging ◽  
Epigenetic Mechanism ◽  
Histone Deacetylase 2 ◽  
Damage Response

Histone deacetylase 2 (HDAC2) is a class I histone deacetylase that regulates various cellular processes, such as cell cycle, senescence, proliferation, differentiation, development, apoptosis, and glucocorticoid function in inhibiting inflammatory response. HDAC2 has been shown to protect against DNA damage response and cellular senescence/premature aging via an epigenetic mechanism in response to oxidative stress. These phenomena are observed in patients with chronic obstructive pulmonary disease (COPD). HDAC2 is posttranslationally modified by oxidative/carbonyl stress imposed by cigarette smoke and oxidants, leading to its reduction via an ubiquitination-proteasome dependent degradation in lungs of patients with COPD. In this perspective, we have discussed the role of HDAC2 posttranslational modifications and its role in regulation of inflammation, histone/DNA epigenetic modifications, DNA damage response, and cellular senescence, particularly in inflammaging, and during the development of COPD. We have also discussed the potential directions for future translational research avenues in modulating lung inflammaging and cellular senescence based on epigenetic chromatin modifications in diseases associated with increased oxidative stress.

scholarly journals DNA damage responses in ageing

Open Biology ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 190168 ◽  
Author(s):  
Paulo F. L. da Silva ◽  
Björn Schumacher
Keyword(s):  
Dna Damage ◽  
Stress Response ◽  
Cellular Senescence ◽  
Damage Accumulation ◽  
Genome Instability ◽  
Age Related ◽  
Progeroid Syndromes ◽  
Dna Damage Responses ◽  
Universal Feature

Ageing appears to be a nearly universal feature of life, ranging from unicellular microorganisms to humans. Longevity depends on the maintenance of cellular functionality, and an organism's ability to respond to stress has been linked to functional maintenance and longevity. Stress response pathways might indeed become therapeutic targets of therapies aimed at extending the healthy lifespan. Various progeroid syndromes have been linked to genome instability, indicating an important causal role of DNA damage accumulation in the ageing process and the development of age-related pathologies. Recently, non-cell-autonomous mechanisms including the systemic consequences of cellular senescence have been implicated in regulating organismal ageing. We discuss here the role of cellular and systemic mechanisms of ageing and their role in ageing-associated diseases.

scholarly journals Studies on the Physiological Role of Hypothalamic TRH on the Negative Feedback Mechanism of the Pituitary-Thyroid Axis

1979 ◽  
Vol 55 (6) ◽  
pp. 776-786
Author(s):  
Masatomo MORI ◽  
Kihachi OHSHIMA ◽  
Sakae MARUTA ◽  
Hitoshi FUKUDA ◽  
Yohnosuke SHIMOMURA ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Physiological Role ◽  
Feedback Mechanism ◽  
Negative Feedback Mechanism ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis

scholarly journals The Role of Angiopoietin-like Protein 3 and Fibroblast Growth Factor 21 to Lipolysis, Inflammation and Insulin Resistance in Indonesian Non-Diabetic Obese Male

2010 ◽  
Vol 2 (2) ◽  
pp. 33
Author(s):  
Yani Lina ◽  
Gatot Susilo Lawrence ◽  
Andi Wijaya ◽  
Suryani As'ad
Keyword(s):  
Insulin Resistance ◽  
Fasting Blood Glucose ◽  
Feedback Mechanism ◽  
Fibroblast Growth Factor 21 ◽  
Low Grade ◽  
Cross Sectional ◽  
Negative Feedback Mechanism ◽  
Two Factors ◽  
Cross Sectional Design

BACKGROUND: Obesity is commonly associated with a systemic low grade inflammation and insulin resistance state. Although it is still being debated, increased lipolysis is known as one of the risk factors for inflammation and insulin resistance. Two factors already known to affect lipolysis are Angptl3, known as prolipolytic factor, and FGF21, known as antilipolytic factor. The aim of this study was to observe the role of Angptl3 and FGF21 to lipolysis, inflammation and insulin resistance in non diabetic obese male.METHODS: This was an observational study with cross sectional design. One hundred and thirty male subjects aged 30-60 years with non diabetic abdominal obesity characterized by waist circumference 97.32±5.63 cm and fasting blood glucose 90.19±8.78 mg/dL.RESULTS: The results of this study showed a correlation between Angptl3-FFA (r=0.203; p=0.021; R square=0.041; p=0.021), Angptl3-FABP4 (r=0.330; p=0.000; R square=0.109; p=0.000) and Angptl3-TNFα (r=0.288; p=0.001; R square=0.049; p=0.011). There was a correlation between FGF21-FABP4 (r=0.218, p=0.013; R square=0.047, p=0.013) and FGF21 HOMA-IR (r=0.308, p=0.000; R square=0.046, p=0.014).CONCLUSIONS: We conclude that Angptl3 may affect lipolysis and inflammation while FGF21 may affect lipolysis and insulin resistance. The increased FGF21 concentration might occur as a compensation (negative feedback mechanism) to reduce lipolysis and increase insulin sensitivity in non diabetic obese males. Further studies might be needed to observe Angptl3 and FGF21 profile in more severe obese population in Indonesia.KEYWORDS: obesity, lipolysis, inflammation, insulin resistance

scholarly journals Relationship of TSH with BMI in subclinical hypothyroid patients

2019 ◽  
Vol 9 (4) ◽  
pp. 4193-4198
Keyword(s):  
Thyroid Hormones ◽  
Negative Correlation ◽  
Subclinical Hypothyroidism ◽  
Inverse Correlation ◽  
Feedback Mechanism ◽  
Negative Feedback Mechanism ◽  
Body Development ◽  
Relationship Of ◽  
The Relationship ◽  
Hypothyroid Patients

Thyroid hormones (T3 and T4) synthesized by thyroid gland and play an essential role in normal body development and tissue metabolism. Iodine is an essential factor that is required for the synthesis of thyroid hormones. The secretion of thyroid hormones is regulated by Negative feedback mechanism. After reached in blood circulation the majority of T4 and T3 bound with carrier proteins called thyroxine binding proteins (TBG) which shows higher affinity for T4. The common diseases related to thyroid hormones include Hypothyroidism, hyperthyroidism, thyroiditis, goiter, nodes, and tumors of thyroid glands (benign and malignant). Subclinical hypothyroidism also called mild thyroid failure is defined as normal thyroid hormones but mildly elevated TSH (5 – 10 uIU/ml) with no or mild sign and symptoms. The thyroid disorders are more prevalent in females than males. Hypothyroidism is associated with obesity and various studies conducted to find out the relationship between TSH and BMI observed different finding in the particular study. In the present study, a poor positive correlation between TSH and BMI was observed in the total euthyroid subjects. A poor negative association between TSH and BMI in euthyroid males and poor positive (r value – 0.21) relationship was observed in euthyroid females. In Subclinical hypothyroid patients (total, male and female), Poor negative correlation was observed between TSH and BMI. The conclusion of this study is, as TSH increased the BMI will also increase in (mostly females) euthyroid subjects. The Inverse or poor negative correlation was observed within TSH and BMI among euthyroid males and an inverse correlation was noticed in patients with subclinical hypothyroidism.

scholarly journals Autolysosomal degradation of cytosolic chromatin fragments antagonizes oxidative stress–induced senescence

2020 ◽  
Vol 295 (14) ◽  
pp. 4451-4463 ◽  
Author(s):  
Xiaojuan Han ◽  
Honghan Chen ◽  
Hui Gong ◽  
Xiaoqiang Tang ◽  
Ning Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cellular Senescence ◽  
Bafilomycin A1 ◽  
Nih3t3 Cells ◽  
Present Evidence ◽  
Chromatin Fragment ◽  
Secretory Phenotype ◽  
Peroxide Stress

Oxidative stress-induced DNA damage, the senescence-associated secretory phenotype (SASP), and impaired autophagy all are general features of senescent cells. However, the cross-talk among these events and processes is not fully understood. Here, using NIH3T3 cells exposed to hydrogen peroxide stress, we show that stress-induced DNA damage provokes the SASP largely via cytosolic chromatin fragment (CCF) formation, which activates a cascade comprising cGMP-AMP synthase (cGAS), stimulator of interferon genes protein (STING), NF-κB, and SASP, and that autolysosomal function inhibits this cascade. We found that CCFs accumulate in senescent cells with activated cGAS-STING-NF-κB signaling, promoting SASP and cellular senescence. We also present evidence that the persistent accumulation of CCFs in prematurely senescent cells is partially associated with a defect in DNA-degrading activity in autolysosomes and reduced abundance of activated DNase 2α. Intriguingly, we found that metformin- or rapamycin-induced activation of autophagy significantly lessened the size and levels of CCFs and repressed the activation of the cGAS-STING-NF-κB-SASP cascade and cellular senescence. These effects of autophagy activators indicated that autolysosomal function contributes to CCF clearance and SASP suppression, further supported by the fact that the lysosome inhibitor bafilomycin A1 blocked the role of autophagy-mediated CCF clearance and senescence repression.

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