scholarly journals Hormonally regulated myogenic miR-486 influences sex-specific differences in cancer-induced skeletal muscle defects

Endocrinology ◽  
2021 ◽  
Author(s):  
Ruizhong Wang ◽  
Poornima Bhat-Nakshatri ◽  
Xiaoling Zhong ◽  
Teresa Zimmers ◽  
Harikrishna Nakshatri
Keyword(s):  
Skeletal Muscle ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Regulatory Region ◽  
Negative Regulator ◽  
C2c12 Myoblast ◽  
Receptor Modulator ◽  
Signaling Axis ◽  
Myoblast Cell Line ◽  
Myoblast Cell

Abstract Cancer-induced skeletal muscle defects show sex-specific differences in severity with men performing poorly compared to women. Hormones and sex chromosomal differences are suggested to mediate these differences, but the functional skeletal muscle markers to document these differences are unknown. We show that the myogenic microRNA miR-486 is a marker of sex-specific differences in cancer-induced skeletal muscle defects. Cancer-induced loss of circulating miR-486 was more severe in men with bladder, lung and pancreatic cancers compared to women with the same cancer types. In syngeneic model of pancreatic cancer, circulating and skeletal muscle loss of miR-486 was more severe in male mice compared to female mice. Estradiol (E2) and the clinically used selective estrogen receptor modulator toremifene increased miR-486 in undifferentiated and differentiated myoblast cell line C2C12 and E2-inducible expression correlated with direct binding of estrogen receptor alpha (ERα) to the regulatory region of miR-486 gene. E2 and toremifene reduced the actions of cytokines such as myostatin, TGFβ and TNFα, which mediate cancer-induced skeletal muscle wasting. E2 and toremifene treated C2C12 myoblast/myotube cells contained elevated levels of active AKT with corresponding decrease in the levels of its negative regulator PTEN, which is a target of miR-486. We propose an ERα:E2-miR-486-AKT signaling axis, which reduces the deleterious effects of cancer-induced cytokines/chemokines on skeletal muscle mass and/or function.

Cartap-induced cytotoxicity in mouse C2C12 myoblast cell line and the roles of calcium ion and oxidative stress on the toxic effects

Toxicology ◽  
2006 ◽  
Vol 219 (1-3) ◽  
pp. 73-84 ◽  
Author(s):  
Jiunn-Wang Liao ◽  
Jaw-Jou Kang ◽  
Chian-Ren Jeng ◽  
Shao-Kuang Chang ◽  
Ming-Jang Kuo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Line ◽  
Calcium Ion ◽  
Toxic Effects ◽  
C2c12 Myoblast ◽  
Myoblast Cell Line ◽  
Myoblast Cell ◽  
And Oxidative Stress

scholarly journals Propofol elicits autophagy via endoplasmic reticulum stress and calcium exchange in C2C12 myoblast cell line

PLoS ONE ◽  
2018 ◽  
Vol 13 (5) ◽  
pp. e0197934 ◽  
Author(s):  
Xi Chen ◽  
Long-Yun Li ◽  
Jin-Lan Jiang ◽  
Kai Li ◽  
Zhen-Bo Su ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Line ◽  
C2c12 Myoblast ◽  
Myoblast Cell Line ◽  
Calcium Exchange ◽  
Myoblast Cell

scholarly journals A Theacrine-Based Supplement Increases Cellular NAD+ Levels and Affects Biomarkers Related to Sirtuin Activity in C2C12 Muscle Cells In Vitro

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3727
Author(s):  
Petey W. Mumford ◽  
Shelby C. Osburn ◽  
Carlton D. Fox ◽  
Joshua S. Godwin ◽  
Michael D. Roberts
Keyword(s):  
Cell Line ◽  
Mitochondrial Biogenesis ◽  
C2c12 Myoblast ◽  
Mrna Levels ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Protein Levels ◽  
Myoblast Cell Line ◽  
Rodent Cell ◽  
Myoblast Cell

There is evidence in rodents to suggest that theacrine-based supplements modulate tissue sirtuin activity as well as other biological processes associated with aging. Herein, we examined if a theacrine-based supplement (termed NAD3) altered sirtuin activity in vitro while also affecting markers of mitochondrial biogenesis. The murine C2C12 myoblast cell line was used for experimentation. Following 7 days of differentiation, myotubes were treated with 0.45 mg/mL of NAD3 (containing ~2 mM theacrine) for 3 and 24 h (n = 6 treatment wells per time point). Relative to control (CTL)-treated cells, NAD3 treatments increased (p < 0.05) Sirt1 mRNA levels at 3 h, as well as global sirtuin activity at 3 and 24 h. Follow-up experiments comparing 24 h NAD3 or CTL treatments indicated that NAD3 increased nicotinamide phosphoribosyltransferase (NAMPT) and SIRT1 protein levels (p < 0.05). Cellular nicotinamide adenine dinucleotide (NAD+) levels were also elevated nearly two-fold after 24 h of NAD3 versus CTL treatments (p < 0.001). Markers of mitochondrial biogenesis were minimally affected. Although these data are limited to select biomarkers in vitro, these preliminary findings suggest that a theacrine-based supplement can modulate select biomarkers related to NAD+ biogenesis and sirtuin activity. However, these changes did not drive increases in mitochondrial biogenesis. While promising, these data are limited to a rodent cell line and human muscle biopsy studies are needed to validate and elucidate the significance of these findings.

scholarly journals In Vitro Effects of Emerging Bisphenols on Myocyte Differentiation and Insulin Responsiveness

2020 ◽  
Vol 178 (1) ◽  
pp. 189-200
Author(s):  
Jiongjie Jing ◽  
Yong Pu ◽  
Almudena Veiga-Lopez ◽  
Lihua Lyu
Keyword(s):  
Skeletal Muscle ◽  
Bisphenol A ◽  
Cell Lines ◽  
Glucose Transporter ◽  
Myogenic Differentiation ◽  
Metabolic Effects ◽  
C2c12 Myoblast ◽  
Short Term Exposure ◽  
Insulin Responsiveness ◽  
Myoblast Cell

Abstract Bisphenols are endocrine disrupting chemicals to which humans are ubiquitously exposed to. Prenatal bisphenol A exposure can lead to insulin resistance. However, the metabolic effects of other emerging bisphenols, such as bisphenol S (BPS) and bisphenol F (BPF), are less understood. Because the skeletal muscle is the largest of the insulin target tissues, the goal of this study was to evaluate the effects of 2 emerging bisphenols (BPS and BPF) on cytotoxicity, proliferation, myogenic differentiation, and insulin responsiveness in skeletal muscle cells. We tested this using a dose-response approach in C2C12 mouse and L6 rat myoblast cell lines. The results showed that C2C12 mouse myoblasts were more susceptible to bisphenols compared with L6 rat myoblasts. In both cell lines, bisphenol A was more cytotoxic, followed by BPF and BPS. C2C12 myoblast proliferation was higher upon BPF exposure at the 10−4 M dose and the fusion index was increased after exposure to either BPF or BPS at doses over 10−10 M. Exposure to BPS and BPF also reduced baseline expression of p-AKT (Thr) and p-GSK-3β, but not downstream effectors such as mTOR and glucose transporter-4. In conclusion, at noncytotoxic doses, BPS and BPF can alter myoblast cell proliferation, differentiation, and partially modulate early effectors of the insulin receptor signaling pathway. However, BPS or BPF short-term exposure evaluated here does not result in impaired insulin responsiveness.

The growth-promoting activity of egg white proteins in the C2C12 myoblast cell line

2014 ◽  
Vol 86 (2) ◽  
pp. 194-199 ◽  
Author(s):  
Wataru Mizunoya ◽  
Ayumi Tashima ◽  
Yusuke Sato ◽  
Ryuichi Tatsumi ◽  
Yoshihide Ikeuchi
Keyword(s):  
Cell Line ◽  
Egg White ◽  
C2c12 Myoblast ◽  
Egg White Proteins ◽  
Myoblast Cell Line ◽  
Growth Promoting ◽  
Myoblast Cell

scholarly journals Aurora kinase A mediated phosphorylation of mPOU is critical for skeletal muscle differentiation

2019 ◽  
Author(s):  
Dhanasekaran Karthigeyan ◽  
Arnab Bose ◽  
Ramachandran Boopathi ◽  
Vinay Jaya Rao ◽  
Hiroki Shima ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Aurora Kinase ◽  
Muscle Differentiation ◽  
Negative Regulator ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Skeletal Muscle Differentiation ◽  
Skeletal Myogenesis ◽  
Aurora Kinase A ◽  
Kinase A

AbstractAurora kinases are Ser/Thr-directed protein kinases which play pivotal roles in mitosis. Recent evidences highlight the importance of these kinases in non-mitotic biological events like skeletal myogenesis. Our earlier study identified POU6F1 (or mPOU) as a novel Aurora kinase A (AurkA) substrate. Here, we report that AurkA phosphorylates POU6F1 at Ser197 and inhibits its DNA binding ability. Delving into POU6F1 physiology, we find that the phospho-mimic (S197D) POU6F1 mutant exhibits enhancement, while wild type (WT) or phospho-deficient (S197A) mutant shows retardation in C2C12 myoblast differentiation. Interestingly, POU6F1 depletion phenocopies S197D-POU6F1 overexpression in the differentiation context. Collectively, our results signify mPOU as a negative regulator of skeletal muscle differentiation and strengthens the importance of AurkA in skeletal myogenesis.

scholarly journals Estetrol: A New Choice for Contraception

2021 ◽  
Vol 10 (23) ◽  
pp. 5625
Author(s):  
Franca Fruzzetti ◽  
Tiziana Fidecicchi ◽  
Maria Magdalena Montt Guevara ◽  
Tommaso Simoncini
Keyword(s):  
Estrogen Receptor ◽  
User Satisfaction ◽  
Large Scale ◽  
Estrogen Receptor Alpha ◽  
Fetal Liver ◽  
Target Population ◽  
Receptor Modulator ◽  
Human Estrogen Receptor ◽  
Synthetic Estrogens ◽  
Orally Bioavailable

Estetrol (E4) is a natural estrogenic steroid that is normally produced by human fetal liver. Recent research has demonstrated that it is a potent, orally bioavailable, natural selective estrogen receptor modulator; it has a moderate affinity for both human estrogen receptor alpha (ERα) and ERβ, with a preference for ERα. Clinical studies have demonstrated possible use as an estrogen in combined oral contraceptives (COC). COCs containing E4 and drospirenone (DRSP) showed a high acceptability, tolerability, and user satisfaction also when compared to COCs containing ethinylestradiol (EE). E4/DRSP effectively inhibits ovulation, with a similar effect on endometrium thickness than that of EE-containing COCs. Low doses (15 mg) of E4 with DRSP (3 mg) showed promising results in term of bleeding pattern and cycle control, also when compared to other COCs containing synthetic estrogens. Moreover, the association has limited effects on serum lipids, liver, SHBG levels, and carbohydrate metabolism. This combination also could drive a lower risk of venous thromboembolism than EE-containing COCs. In this review, we will summarize the actual knowledge about the new E4-containing contraceptive. Further large-scale studies in the full target population are needed to provide more insights into the cardiovascular safety profile and user satisfaction of E4/DRSP.

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