Molecular and Cellular Biochemistry

, Volume 312, Issue 1–2, pp 17–24

Protein–DNA array-based identification of transcription factor activities differentially regulated in skeletal muscle of normal and dystrophin-deficient mdx mice

  • Charu Dogra
  • Daya Shankar Srivastava
  • Ashok Kumar
Article

DOI: 10.1007/s11010-008-9716-6

Cite this article as:
Dogra, C., Srivastava, D.S. & Kumar, A. Mol Cell Biochem (2008) 312: 17. doi:10.1007/s11010-008-9716-6

Abstract

Inactivation of dystrophin gene is the primary cause of Duchenne muscular dystrophy (DMD) in humans and mdx mice. However, the underpinning mechanisms, which govern the pathogenesis of dystrophin-deficient skeletal muscle, remain poorly understood. We have previously reported activation of mitogen-activated protein kinases (MAPK), nuclear factor-kappa B (NF-κB), and phosphatidyl-inositol 3-kinase/Akt (PI3K/Akt) signaling pathways in diaphragm muscle of mdx mice. In this study, using a protein–DNA array-based approach, we have investigated the activation of 345 transcription factors in diaphragm muscle of 6-week old normal and dystrophin-deficient mdx mice. Our data demonstrate increased activation of a number nuclear transcription factors including AP1, HFH-3, PPARα, c.myb BP, ETF, Fra-1/JUN, kBF-A, N-rasBP, lactoferrin BP, Myb(2), EBP40_45, EKLF(1), p53(2), TFEB, Myc-Max; c-Rel; E2, ISRE; NF-kB; Stat1 p84/p91, Antioxidant RE, EVI-1, Stat3, AP3, p53, Stat4, AP4, HFH-1, FAST-1, Pax-5, and Beta-RE in the diaphragm muscle of mdx mice compared to corresponding normal mice. The level of activation for p53 was highest among all the transcription factors studied. Furthermore, higher activation of p53 in diaphragm muscle of mdx mice was associated with its increased phosphorylation and nuclear translocation. Collectively, our data suggest that the primary deficiency of dystrophin leads to the aberrant activation of nuclear transcription factors which might further contribute to muscle pathogenesis in mdx mice.

Keywords

Protein–DNA array Transcription factors Dystrophin Mdx NF-kappa B 

Abbreviations

AP-1

Activator protein-1

DMD

Duchenne muscular dystrophy

EMSA

Electrophoretic mobility shift assay

NF-κB

Nuclear factor-kappa B

PI3K

Phosphatidyl-inositol 3-kinase

STAT

Signal transduction and activator of transcription

Supplementary material

11010_2008_9716_MOESM1_ESM.pdf (864 kb)
(PDF 864 kb)

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Charu Dogra
    • 1
  • Daya Shankar Srivastava
    • 2
  • Ashok Kumar
    • 1
    • 2
  1. 1.Musculoskeletal Disease CenterJerry L. Pettis Memorial Veteren Affairs Medical CenterLoma LindaUSA
  2. 2.Department of Anatomical Sciences and NeurobiologyUniversity of Louisville School of MedicineLouisvilleUSA

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