T‐type calcium channel blockade induces apoptosis in C2C12 myotubes and skeletal muscle via endoplasmic reticulum stress activation

Chen, Mao; Li, Suting; Hao, Meng-lei; Chen, Jue; Zhao, Zhihan; Hong, Shasha; Min, Jie; Tang, Jianming; Hu, Ming; Li, Hong

doi:10.1002/2211-5463.12965

Cited by 8 publications

(9 citation statements)

References 36 publications

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“…For instance, calcium release from the endoplasmic reticulum can also induce inner mitochondrial pathway of apoptosis in a variety of cells [ 42 ]. As well, in skeletal muscle cells, T-type Ca 2+ channels can induce endoplasmic reticulum Ca 2+ disorder, contributing to mitochondrial-related apoptosis [ 43 ]. In this regard, the role of Ca 2 + -release channel, ryanodine receptor (RyR) and inositol trisphosphate receptor (IP3R), other than T-type Ca 2+ channels, have been extensively studied in the regulation of apoptosis in different preparations [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow-Mesenchymal Stromal Cell Secretome as Conditioned Medium Relieves Experimental Skeletal Muscle Damage Induced by Ex Vivo Eccentric Contraction

Squecco

Tani

Chellini

et al. 2021

IJMS

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Bone marrow-mesenchymal stem/stromal cells (MSCs) may offer promise for skeletal muscle repair/regeneration. Growing evidence suggests that the mechanisms underpinning the beneficial effects of such cells in muscle tissue reside in their ability to secrete bioactive molecules (secretome) with multiple actions. Hence, we examined the effects of MSC secretome as conditioned medium (MSC-CM) on ex vivo murine extensor digitorum longus muscle injured by forced eccentric contraction (EC). By combining morphological (light and confocal laser scanning microscopies) and electrophysiological analyses we demonstrated the capability of MSC-CM to attenuate EC-induced tissue structural damages and sarcolemnic functional properties’ modifications. MSC-CM was effective in protecting myofibers from apoptosis, as suggested by a reduced expression of pro-apoptotic markers, cytochrome c and activated caspase-3, along with an increase in the expression of pro-survival AKT factor. Notably, MSC-CM also reduced the EC-induced tissue redistribution and extension of telocytes/CD34+ stromal cells, distinctive cells proposed to play a “nursing” role for the muscle resident myogenic satellite cells (SCs), regarded as the main players of regeneration. Moreover, it affected SC functionality likely contributing to replenishment of the SC reservoir. This study provides the necessary groundwork for further investigation of the effects of MSC secretome in the setting of skeletal muscle injury and regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Bone Marrow-Mesenchymal Stromal Cell Secretome as Conditioned Medium Relieves Experimental Skeletal Muscle Damage Induced by Ex Vivo Eccentric Contraction

Squecco

Tani

Chellini

et al. 2021

IJMS

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“…Chen et al ( 2020 ) reported that TCC blockade (in C2C12 myoblasts) induced mitochondria‐related apoptosis and reduced mitochondrial transmembrane potential (MMP), induced mito‐ROS generation and enhanced expression of mitochondrial apoptosis proteins.…”

Section: Assessmentmentioning

confidence: 99%

“…They suggested that this highaffinity low-efficacy inhibition may be caused by direct binding of BPA to TCCs in their resting state. Chen et al (2020) reported that TCC blockade (in C2C12 myoblasts) induced mitochondria-related apoptosis and reduced mitochondrial transmembrane potential (MMP), induced mito-ROS generation and enhanced expression of mitochondrial apoptosis proteins. ] reported BPA-related decreased activities of mitochondrial respiratory complexes and abnormalities in mitochondrial morphology in rat cardiac myofibrils, including decreased mitochondrial volume density, reduced cristae density and increased vacuoles, after low-dose BPA (50 μg/kg bw per day) for 48 weeks.…”

Section: Neuromorphologymentioning

confidence: 99%

Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

Lambré¹,

Baviera²,

Bolognesi³

et al. 2023

EFS2

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In 2015, EFSA established a temporary tolerable daily intake (t‐TDI) for BPA of 4 μg/kg body weight (bw) per day. In 2016, the European Commission mandated EFSA to re‐evaluate the risks to public health from the presence of BPA in foodstuffs and to establish a tolerable daily intake (TDI). For this re‐evaluation, a pre‐established protocol was used that had undergone public consultation. The CEP Panel concluded that it is Unlikely to Very Unlikely that BPA presents a genotoxic hazard through a direct mechanism. Taking into consideration the evidence from animal data and support from human observational studies, the immune system was identified as most sensitive to BPA exposure. An effect on Th17 cells in mice was identified as the critical effect; these cells are pivotal in cellular immune mechanisms and involved in the development of inflammatory conditions, including autoimmunity and lung inflammation. A reference point (RP) of 8.2 ng/kg bw per day, expressed as human equivalent dose, was identified for the critical effect. Uncertainty analysis assessed a probability of 57–73% that the lowest estimated Benchmark Dose (BMD) for other health effects was below the RP based on Th17 cells. In view of this, the CEP Panel judged that an additional uncertainty factor (UF) of 2 was needed for establishing the TDI. Applying an overall UF of 50 to the RP, a TDI of 0.2 ng BPA/kg bw per day was established. Comparison of this TDI with the dietary exposure estimates from the 2015 EFSA opinion showed that both the mean and the 95th percentile dietary exposures in all age groups exceeded the TDI by two to three orders of magnitude. Even considering the uncertainty in the exposure assessment, the exceedance being so large, the CEP Panel concluded that there is a health concern from dietary BPA exposure.

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“…Severe and prolonged ERS leads to cell death. The VGCC inhibitors, verapamil and mibefradil were reported to facilitate cell death via ERS activation in myeloma cells and C2C12 myoblasts [151,152]. Furthermore, progesterone inhibited cell growth and promoted apoptosis via CACNA2D3 in Ishikawa cells [73].…”

Section: Potential Applications Of Calcium Channel Modulators For Cancer Treatmentmentioning

confidence: 99%

Calcium and calcium-related proteins in endometrial cancer: opportunities for pharmacological intervention

Huang¹,

Zhou²,

Wang³

2022

Int. J. Biol. Sci.

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Intracellular calcium ions are key second messengers and play an important role in malignant transformation and cancer progression. Estrogen can evoke intracellular calcium increases through membrane-initiated effects and activate subsequent kinase cascades within minutes in normal and cancerous epithelial cells. Ca 2+ -related proteins are expressed in normal epithelial cells or endometrial cancer cells, some of which are upregulated by estrogen. Both estrogen-induced transient calcium increases and long-term changes in protein expression levels may be involved in regulating cancer initiation, progression and metastasis. Calcium channel blockers are reported to regulate both the rapid estrogen-induced intracellular Ca 2+ increase and cell proliferation, apoptosis and migration, thus having the potential for pharmacological modulators to be repurposed for the treatment of endometrial cancer.

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T‐type calcium channel blockade induces apoptosis in C2C12 myotubes and skeletal muscle via endoplasmic reticulum stress activation

Cited by 8 publications

References 36 publications

Bone Marrow-Mesenchymal Stromal Cell Secretome as Conditioned Medium Relieves Experimental Skeletal Muscle Damage Induced by Ex Vivo Eccentric Contraction

Bone Marrow-Mesenchymal Stromal Cell Secretome as Conditioned Medium Relieves Experimental Skeletal Muscle Damage Induced by Ex Vivo Eccentric Contraction

Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

Calcium and calcium-related proteins in endometrial cancer: opportunities for pharmacological intervention

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