The ERG1A K+ Channel Is More Abundant in Rectus abdominis Muscle from Cancer Patients Than that from Healthy Humans

Background: The potassium channel encoded by the ether-a-gogo-related gene 1A (erg1a) has been detected in the atrophying skeletal muscle of mice experiencing either muscle disuse or cancer cachexia and further evidenced to contribute to muscle deterioration by enhancing ubiquitin proteolysis; however, to our knowledge, ERG1A has not been reported in human skeletal muscle. Methods and Results: Here, using immunohistochemistry, we detect ERG1A immunofluorescence in human Rectus abdominis skeletal muscle sarcolemma. Further, using single point brightness data, we report the detection of ERG1A immunofluorescence at low levels in the Rectus abdominis muscle sarcolemma of young adult humans and show that it trends toward greater levels (10.6%) in healthy aged adults. Interestingly, we detect ERG1A immunofluorescence at a statistically greater level (53.6%; p < 0.05) in the skeletal muscle of older cancer patients than in age-matched healthy adults. Importantly, using immunoblot, we reveal that lower mass ERG1A protein is 61.5% (p < 0.05) more abundant in the skeletal muscle of cachectic older adults than in healthy age-matched controls. Additionally, we report that the ERG1A protein is detected in a cultured human rhabdomyosarcoma line that may be a good in vitro model for the study of ERG1A in muscle. Conclusions: The data demonstrate that ERG1A is detected more abundantly in the atrophied skeletal muscle of cancer patients, suggesting it may be related to muscle loss in humans as it has been shown to be in mice experiencing muscle atrophy as a result of malignant tumors.

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The ERG1 Potassium Channel is More Abundant in Skeletal Muscle from Cachectic than Healthy Humans

10.21203/rs.3.rs-17510/v1 ◽

2020 ◽

Author(s):

Sandra Zampieri ◽

Marco Sandri ◽

Joseph L. Cheatwood ◽

Rajesh P. Balaraman ◽

Luke B. Anderson ◽

...

Keyword(s):

Skeletal Muscle ◽

Potassium Channel ◽

Cancer Cachexia ◽

Single Point ◽

Rectus Abdominis ◽

Calcium Handling ◽

Healthy Humans ◽

Muscle Disuse ◽

Fluorescent Pattern ◽

Low Levels

Abstract Background: The ERG1a potassium channel has been detected in the atrophying skeletal muscle of mice experiencing either muscle disuse or cancer cachexia and further evidenced to contribute to muscle deterioration by enhancing ubiquitin proteolysis; however, to our knowledge, ERG1 has not been reported in human skeletal muscle. Methods and Results: Here, using immunohistochemistry, we detect ERG1 immunofluorescence in human Rectus abdominis skeletal muscle sarcolemma. Further, using single point brightness data, we report detection of ERG1 immunofluorescence at low levels in the Rectus abdominis muscle sarcolemma of young adult humans and show that it trends toward greater levels (10.6%) in healthy aged adults. Interestingly, we detect ERG1 immunofluorescence at a statistically greater level (53.6%; p<0.05) in the skeletal muscle of older people having cancer cachexia than in age-matched adults. Importantly, using immunoblot, we reveal that ERG1 protein is 38% (p<0.09) more abundant in the skeletal muscle of cachectic older adults than in healthy age-matched controls. Additionally, we report that the ERG1 fluorescent pattern is consistent with I-band localization. Conclusions: The data suggest that ERG1 may be related to muscle loss in humans and is located in t-tubules where it could influence calcium handling.

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Repression of Matrix Metalloproteinases and Cytokine Secretion in Glioblastoma by Targeting K+ Channel: An in Vitro Study

Basic and Clinical Neuroscience Journal ◽

10.32598/bcn.2021.1693.1 ◽

2021 ◽

Author(s):

Farshid Saadat ◽

◽

Zohreh Zareighane ◽

Farnaz Safavifar ◽

Seyedeh Zohreh Jalali ◽

...

Keyword(s):

Matrix Metalloproteinases ◽

Cell Viability ◽

Malignant Tumors ◽

Cell Model ◽

Gelatin Zymography ◽

In Vitro Study ◽

K Channel ◽

Kv Channels ◽

Vitro Model

Introduction: Glioblastoma is an aggressive malignancy of human brain with poorly understood pathogenesis. Voltage-gated potassium (Kv) channels and Matrix metalloproteinases (MMPs) are highly expressed in malignant tumors and involved in the progression and metastasis of glioblastoma. The purpose of this study was to determine whether a voltage-dependent potassium channel blocker could modulate astrocytes as a cell which involved in immunopathogenesis of glioblastoma. Methods: The cytotoxic effect of 4-aminopyridine (4-AP) at different doses in cell model of glioblastoma was measured by MTT assay. ELISA technique and gelatin zymography were used to assess cytokines levels and MMP-9 after 4-AP treatment, respectively. Results: Cytotoxicity analysis showed that cell viability reduced by increasing 4-AP level and cell growth reduced gradually by removing 4-AP from cell medium. 4-AP inhibits secretion of IL-6 and IL-1 (p<0.05). MMP9 activity significantly inhibits with increased 4-AP dose as compared to non-treated cells. Conclusion: Reduction of cell viability, IL-6 secretion and MMP-9 activity in an in vitro model of glioblastoma, might be assumed 4-AP as an agent for chemoprevention of cancer.

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Engineering a 3D in vitro model of human skeletal muscle at the single fiber scale

PLoS ONE ◽

10.1371/journal.pone.0232081 ◽

2020 ◽

Vol 15 (5) ◽

pp. e0232081 ◽

Cited By ~ 2

Author(s):

Anna Urciuolo ◽

Elena Serena ◽

Rusha Ghua ◽

Susi Zatti ◽

Monica Giomo ◽

...

Keyword(s):

Skeletal Muscle ◽

Human Skeletal Muscle ◽

In Vitro Model ◽

Single Fiber ◽

3D In Vitro Model ◽

Vitro Model

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Skeletal muscle-on-a-chip: an in vitro model to evaluate tissue formation and injury

Lab on a Chip ◽

10.1039/c7lc00512a ◽

2017 ◽

Vol 17 (20) ◽

pp. 3447-3461 ◽

Cited By ~ 46

Author(s):

Gaurav Agrawal ◽

Aereas Aung ◽

Shyni Varghese

Keyword(s):

Skeletal Muscle ◽

Muscle Injury ◽

In Vitro Model ◽

Three Dimensional ◽

Tissue Formation ◽

Microfluidic Platform ◽

Muscle Tissues ◽

Vitro Model

We introduce a microfluidic platform in which we culture three-dimensional skeletal muscle tissues, while evaluating tissue formation and toxin-induced muscle injury.

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Cadherins Promote Skeletal Muscle Differentiation in Three-dimensional Cultures

The Journal of Cell Biology ◽

10.1083/jcb.138.6.1323 ◽

1997 ◽

Vol 138 (6) ◽

pp. 1323-1331 ◽

Cited By ~ 84

Author(s):

Ann Redfield ◽

Marvin T. Nieman ◽

Karen A. Knudsen

Keyword(s):

Skeletal Muscle ◽

Cell Adhesion ◽

Three Dimensional ◽

Muscle Differentiation ◽

Skeletal Muscle Differentiation ◽

Skeletal Myogenesis ◽

Bhk Cells ◽

Vitro Model ◽

Cell Cell

The cell–cell adhesion molecule N-cadherin, with its associated catenins, is expressed by differentiating skeletal muscle and its precursors. Although N-cadherin's role in later events of skeletal myogenesis such as adhesion during myoblast fusion is well established, less is known about its role in earlier events such as commitment and differentiation. Using an in vitro model system, we have determined that N-cadherin– mediated adhesion enhances skeletal muscle differentiation in three-dimensional cell aggregates. We transfected the cadherin-negative BHK fibroblastlike cell line with N-cadherin. Expression of exogenous N-cadherin upregulated endogenous β-catenin and induced strong cell–cell adhesion. When BHK cells were cultured as three-dimensional aggregates, N-cadherin enhanced withdrawal from the cell cycle and stimulated differentiation into skeletal muscle as measured by increased expression of sarcomeric myosin and the 12/101 antigen. In contrast, N-cadherin did not stimulate differentiation of BHK cells in monolayer cultures. The effect of N-cadherin was not unique since E-cadherin also increased the level of sarcomeric myosin in BHK aggregates. However, a nonfunctional mutant N-cadherin that increased the level of β-catenin failed to promote skeletal muscle differentiation suggesting an adhesion-competent cadherin is required. Our results suggest that cadherin-mediated cell–cell interactions during embryogenesis can dramatically influence skeletal myogenesis.

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