Role of SIRT3 in Microgravity Response: A New Player in Muscle Tissue Recovery

Aventaggiato, Michele; Barreca, Federica; Vitiello, Laura; Vespa, Simone; Rotili, Dante; Mai, Antonello; Lotti, Lavinia Vittoria; Sansone, Luigi; Russo, Matteo Antonio; Bizzarri, Mariano; Ferretti, Elisabetta; Tafani, Marco

doi:10.3390/cells12050691

Cited by 3 publications

(2 citation statements)

References 77 publications

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“…MyoD is necessary for cells’ commitment to the myogenesis program, while myogenin takes part in the execution of the differentiation [ 33 ]. Moreover, another crucial marker in muscle cell differentiation is MHC, a late differentiation marker and it is part of the sarcomeric structure of skeletal muscle [ 34 ]. A recent article from Raimann et al [ 16 ] showed that the exposure of muscle cells to high levels of phosphate induced an impairment of differentiation process, by reducing MyoD, myogenin, and MHC expression.…”

Section: Discussionmentioning

confidence: 99%

Hypocalcemia in combination with hyperphosphatemia impairs muscle cell differentiation in vitro

Bimonte,

Catanzaro,

Spinello

et al. 2023

J Endocrinol Invest

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Purpose Hypoparathyroidism is a rare endocrine disorder characterized by low or absent secretion of parathyroid hormone (PTH), which leads to decreased calcium and increased phosphorus levels in the serum. The diagnosis of hypoparathyroidism is based on the identification of the aforementioned biochemical abnormalities, which may be accompanied by clinical manifestations. Symptoms of hypoparathyroidism, primarily attributed to hypocalcemia, include muscle cramps or spasms, facial, leg, and foot pain, seizures, and tingling in the lips or fingers. The treatment of hypoparathyroidism depends on the severity of symptoms and the underlying pathology. Over the long term, calcium supplements, active vitamin D analogs, and thiazide diuretics may be needed. In fact, in patient cohorts in which optimal disease control still remains elusive, replacement therapy with recombinant parathyroid hormone analogs may be contemplated. Despite the predominantly neuromuscular symptoms of hypoparathyroidism, further effects of parathyroid hormone deficiency at the muscle cell level remain poorly understood. Thus, the aim of our study was to evaluate the effects of hypocalcemia in combination with hyperphosphatemia on muscle cells differentiation in vitro. Methods C2C12 cells, an in vitro model of muscle cells, were differentiated for 2 or 6 days in the presence of hypocalcemia (CaCl2 0.9 mmol/l) and moderate (PO4 1.4 mmol/l) or severe (PO4 2.9 mmol/l) hyperphosphatemia, or combinations of both conditions. Cell differentiation and expression of genes linked to muscle differentiation were evaluated. Results The combination of hypocalcemia with hyperphosphatemia induced a significant reduction (50%) in differentiation marker levels, such as MyoD (protein 1 for myoblast determination) and myogenin on the 1st day of differentiation, and MHC (myosin heavy chains) after 6 days of differentiation compared to control. Furthermore, this condition induced a statistically significant reduction of insulin-like growth factor-1 (IGF-1) mRNA expression and inhibition of IGF signaling and decrease in ERK phosphorylation compared to control cells. Conclusions Our results showed that a condition of hypocalcemia with hyperphosphatemia induced an alteration of muscle cell differentiation in vitro. In particular, we observed the reduction of myogenic differentiation markers, IGF-1 signaling pathway, and ERK phosphorylation in differentiated skeletal myoblasts. These data suggest that this altered extracellular condition might contribute to the mechanisms causing persistence of symptoms in patients affected by hypoparathyroidism.

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Section: Discussionmentioning

confidence: 99%

Hypocalcemia in combination with hyperphosphatemia impairs muscle cell differentiation in vitro

Bimonte,

Catanzaro,

Spinello

et al. 2023

J Endocrinol Invest

View full text Add to dashboard Cite

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“…Consequently, reducing the musculoskeletal system damage caused by exposure to microgravity is of substantial importance for promoting the development of space exploration. Moreover, recent studies have determined that activating SIRT3 induces mitochondrial autophagy in myoblasts (C2C12) and reduces C2C12 death induced by microgravity, maintaining the expression of C2C12 differentiation markers ( Aventaggiato et al, 2023 ), which suggests that activating SIRT3 may reduce muscle tissue damage caused by microgravity. Notably, muscles and bones are closely related, and together, they constitute the musculoskeletal regulatory system, integrating relevant biological functions.…”

Section: Mechanisms Underlying Sirt3 Regulation Of Bone Homeostasismentioning

confidence: 99%

Role of SIRT3 in bone homeostasis and its application in preventing and treating bone diseases

Xu,

Li,

Wen

et al. 2023

Front. Pharmacol.

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Bone homeostasis refers to the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption and the maintenance of stable bone mass. SIRT3 is a class of mitochondrial protein deacetylase that influences various mitochondrial functions and is involved in the mechanisms underlying resistance to aging; regulation of bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts; and development of osteoporosis, osteoarthritis, and other bone diseases. Moreover, exercise affects bones through SIRT3. Thus, studies on SIRT3 may provide insights for the treatment of bone diseases. Although SIRT3 can exert multiple effects on bone, the specific mechanism by which it regulates bone homeostasis remains unclear. By evaluating the relevant literature, this review discusses the structure and function of SIRT3, reveals the role and associated mechanisms of SIRT3 in regulating bone homeostasis and mediating bone health during exercise, and highlights the potential pharmacological value of SIRT3 in treating bone diseases.

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Gender and age peculiarities of autophagy in men and women induced by a comprehensive wellness program: a prospective observational study

Tkhakushinov,

Lysenkov,

Korchazhkina

et al. 2024

Kuban. nauсh. med. vestnik

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Background. Autophagy refers to an evolutionary physiological mechanism of cell self-purification. The use of its positive effects in regenerative and preventive medicine implies this process to be investigated under the conditions of various therapeutic factors.Objective. To investigate the influence of gender, age and somatic-morphological factors on the autophagy processes induced by a comprehensive wellness program as expressed by the marker protein Beclin-1.Methods. A prospective observational study involved 107 patients to be monitored before and after comprehensive wellness procedures. All study participants underwent a wellness program in the clinic of OOO Centr Zdorovie (Maykop, Russia). The study was conducted in the periods of September‒December 2020 and January 2021. The study involved measuring the concentration of Beclin-1 protein in the blood before and 12 days after the wellness procedures. In order to characterize the degree of activation of the autophagy process, the index “delta-Beclin-1” was introduced (difference between the initial level of Beclin-1 protein concentration and the level registered after 12 days). The autophagy response was evaluated in terms of its upward or downward direction (positive/negative delta- Beclin-1 value, respectively). The effect of the comprehensive wellness procedures on the functional systems of the organism was determined in accordance with the laboratory tests (complete blood count, lipid profile), morphometric evaluation, and the assessment of body composition by impedance monitoring. The obtained data were processed using SPSS Statistics 26.0 (IBM, USA).Results. Monitoring of Beclin-1 protein concentration revealed that basic autophagy activity is age-specific and significantly lower in individuals over 60 years as compared to both individuals under 60 years and healthy persons. This correlation with age appears more pronounced in obese individuals (r = -0.59). The basic activity of autophagy in men was 30% lower than in women, however, after a set of wellness procedures the mentioned response in men increased by 7%. The study found that not all patients responded unidirectionally to the comprehensive wellness procedures: 49 out of 77 patients showed an increase in Beclin-1 protein concentration, while 28 — a decrease. Patients who participated in the wellness program demonstrated negative correlation between the level of Beclin-1 protein expression and age, while those responding with an increase in Beclin-1 protein level — with body mass index, weight and fat mass. The source of autophagy activity in men under 60 years can refer to fat mass, and in women — lean body mass, especially in the mature age of period II (36‒60 years).Conclusion. The factors of basic autophagy and autophagy induced by the complex of wellness procedures include age, gender and body weight. These factors obtain different significance at different age periods. A comprehensive wellness program can serve as an alternative to existing pharmacological methods for activating autophagy in humans.

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Role of SIRT3 in Microgravity Response: A New Player in Muscle Tissue Recovery

Cited by 3 publications

References 77 publications

Hypocalcemia in combination with hyperphosphatemia impairs muscle cell differentiation in vitro

Hypocalcemia in combination with hyperphosphatemia impairs muscle cell differentiation in vitro

Role of SIRT3 in bone homeostasis and its application in preventing and treating bone diseases

Gender and age peculiarities of autophagy in men and women induced by a comprehensive wellness program: a prospective observational study

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