Corticosteroid effects in skeletal muscle: Gene induction/receptor autoregulation

McKay, Lorraine I.; DuBois, Debra C.; Sun, Yu‐Nien; Almon, Richard R.; Jusko, William J.

doi:10.1002/(sici)1097-4598(199710)20:10<1318::aid-mus17>3.0.co;2-z

Cited by 20 publications

(16 citation statements)

References 17 publications

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“…Muscle samples (gastrocnemius) were obtained from a previously performed animal study in our laboratory [2,3,10]. Male adrenalectomized (ADX) Wistar rats (Rattus rattus) weighing 225-250 g were obtained from Harlan Sprague-Dawley (Indianapolis, IN, USA).…”

Section: Experimental Designmentioning

confidence: 99%

“…However, this class of drugs has a low therapeutic index due to a multiplicity of adverse effects on many tissues, including skeletal muscle [1][2][3][4][5][6][7][8][9]. The adverse effects on skeletal muscle derive from the role of this tissue in glucose homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“…These transcriptional effects take two fundamental forms, a direct and indirect method. Many regulated genes contain glucocorticoid responsive elements (GREs) in their regulatory sequences and their transcription is influenced directly [2,3,10,[13][14][15][16][17]. However, there are a large number of genes whose transcription is altered indirectly by glucocorticoids.…”

Section: Introductionmentioning

confidence: 99%

“…In these cases, glucocorticoids alter the expression or function of other transcription factors, which in turn alter the transcription of other genes [13,[18][19][20][21][22]. Although still not entirely understood, the phenomena of muscle wasting and insulin resistance clearly involve temporal cascades of changes in the expression of a multiplicity of genes [2][3][4][5]19,[23][24][25][26]. Many genes involved in the phenomena of muscle wasting and insulin resistance have been identified in a piecemeal fashion using diverse in vitro and in vivo experimental systems.…”

Section: Introductionmentioning

confidence: 99%

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The Genomic Response of Skeletal Muscle to Methylprednisolone Using Microarrays: Tailoring Data Mining to the Structure of the Pharmacogenomic Time Series

Almon

DuBois

Piel

et al. 2004

pgs

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High-throughput data collection using gene microarrays has great potential as a method for addressing the pharmacogenomics of complex biological systems. Similarly, mechanism-based pharmacokinetic/pharmacodynamic modeling provides a tool for formulating quantitative testable hypotheses concerning the responses of complex biological systems. As the response of such systems to drugs generally entails cascades of molecular events in time, a time series design provides the best approach to capturing the full scope of drug effects. A major problem in using microarrays for highthroughput data collection is sorting through the massive amount of data in order to identify probe sets and genes of interest. Due to its inherent redundancy, a rich time series containing many time points and multiple samples per time point allows for the use of less stringent criteria of expression, expression change and data quality for initial filtering of unwanted probe sets. The remaining probe sets can then become the focus of more intense scrutiny by other methods, including temporal clustering, functional clustering and pharmacokinetic/pharmacodynamic modeling, which provide additional ways of identifying the probes and genes of pharmacological interest.

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Section: Experimental Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Genomic Response of Skeletal Muscle to Methylprednisolone Using Microarrays: Tailoring Data Mining to the Structure of the Pharmacogenomic Time Series

Almon

DuBois

Piel

et al. 2004

pgs

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“…Glucocorticoids are the sole drugs used clinically to delay progression in DMD, improving strength and functional outcome, 29 but they have considerable side effects with chronic use. 30,31 Their mechanism of action in dystrophic muscle is far from clear, but comprises a generalized stabilizing effect on myofibers and a reduction of necrosis, likely via their antiinflammatory action.…”

mentioning

confidence: 99%

Effects of prednisolone on the dystrophin-associated proteins in the blood–brain barrier and skeletal muscle of dystrophic mdx mice

Tamma

Annese

Capogrosso

et al. 2013

Laboratory Investigation

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The mdx mouse, the most widely used animal model of Duchenne muscular dystrophy (DMD), develops a seriously impaired blood-brain barrier (BBB). As glucocorticoids are used clinically to delay the progression of DMD, we evaluated the effects of chronic treatment with a-methyl-prednisolone (PDN) on the expression of structural proteins and markers in the brain and skeletal muscle of the mdx mouse. We analyzed the immunocytochemical and biochemical expression of four BBB markers, including endothelial ZO-1 and occludin, desmin in pericytes, and glial fibrillary acidic protein (GFAP) in glial cells, and the expression of the short dystrophin isoform Dp 71, the dystrophin-associated proteins (DAPs), and aquaporin-4 (AQP4) and a-b dystroglycan (DG) in the brain. We evaluated the BBB integrity of mdx and PDN-treated mdx mice by means of intravascular injection of horseradish peroxidase (HRP). The expression of DAPs was also assessed in gastrocnemius muscles and correlated with utrophin expression, and laminin content was measured in the muscle and brain. PDN treatment induced a significant increase in the mRNA and protein content of the BBB markers; a reduction in the phosphorylation of occludin in the brain and of AQP4/b DG in both tissues; an increase of Dp71 protein content; and an increase of both mRNA and protein levels of the AQP4/a-b DG complex. The latter was associated with enhanced laminin and utrophin in the muscle. The HRP assay demonstrated functional restoration of the BBB in the PDN-treated mdx mice. Specifically, mdx mice showed extensive perivascular labeling due to escape of the marker, while HRP was exclusively intravascular in the PDN-treated mice and the controls. These data illustrate for the first time that PDN reverses the BBB alterations in the mdx mouse and re-establishes the proper expression and phosphorylation of b-DG in both the BBB and skeletal muscle. Further, PDN partially protects against muscle damage. The reduction in AQP4 and occludin phosphorylation, coupled with their anchoring to glial and endothelial membranes in PDN-treated mice, suggests that the drug may target the glial and endothelial cells. Our results suggest a novel mechanism for PDN action on cerebral and muscular function, restoring the link between DAPs and the extracellular matrix, most likely through protein kinase inactivation.

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Colorimetric Detection of Glutamine Synthetase-Catalyzed Transferase Activity in Glucocorticoid-Treated Skeletal Muscle Cells

Santoro

Harris

Sitlani

2001

Analytical Biochemistry

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Corticosteroid effects in skeletal muscle: Gene induction/receptor autoregulation

Cited by 20 publications

References 17 publications

The Genomic Response of Skeletal Muscle to Methylprednisolone Using Microarrays: Tailoring Data Mining to the Structure of the Pharmacogenomic Time Series

The Genomic Response of Skeletal Muscle to Methylprednisolone Using Microarrays: Tailoring Data Mining to the Structure of the Pharmacogenomic Time Series

Effects of prednisolone on the dystrophin-associated proteins in the blood–brain barrier and skeletal muscle of dystrophic mdx mice

Colorimetric Detection of Glutamine Synthetase-Catalyzed Transferase Activity in Glucocorticoid-Treated Skeletal Muscle Cells

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