αB-crystallin, a small heat shock protein, modulates NF-ΚB activity in a phosphorylation-dependent manner and protects muscle myoblasts from TNF-α induced cytotoxicity

Amit S. Adhikari, Bhairab N. Singh, K. Sridhar Rao, Ch Mohan Rao

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46 Scopus citations

Abstract

αB-crystallin, a member of the small heat shock protein family, has been implicated in various biological functions including response to heat shock, differentiation and apoptosis, the mechanisms of which have not been well understood. Myoblasts, the precursor cells in muscle regeneration, when subjected to growth factor deprivation differentiate to form myotubes or undergo apoptosis. During differentiation, myoblasts express elevated levels of αB-crystallin as well as TNF-α but the connecting link between these proteins in cell signaling is not clearly understood. We have therefore investigated the role of αB-crystallin in TNF-α induced regulation of NF-ΚB.We demonstrate that in response to TNF-Κ treatment, αB-crystallin associates with IKKβ and activate its kinase activity, facilitating the degradation of phosphorylated I-kBα, a prime step in NF-ΚB activation. Reducing the level of αB-crystallin using the RNAi approach reduces the translocation of p65, further confirming the role of αB-crystallin in NF-ΚB activation. Our study shows that the ability of αB-crystallin to activate NF-ΚB depends on its phosphorylation status. The present study shows that αB-crystallin-dependent NF-αB activation protects myoblasts from TNF-α induced cytoxicity by enhancing the expression of the anti-apoptotic protein, Bcl 2. Thus, our study identifies yet another mechanism by which αB-crystallin exerts its anti-apoptotic activity.

Original languageEnglish (US)
Pages (from-to)1532-1542
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1813
Issue number8
DOIs
StatePublished - Aug 2011

Bibliographical note

Funding Information:
We thank Dr. T. Ramakrishna Murti and Dr. B. Raman for their critical review of the manuscript and invaluable suggestions and Mrs. R. Nandini for help with image analysis. We thank Dr. B. Madhuri for her help in repeating some critical experiments. The help from Dr. Aftab Taiyab in the preparation of this manuscript is acknowledged. Amit S. Adhikari acknowledges the UGC, New Delhi, India for the grant of Senior Research Fellowship. CMR acknowledges the JC Bose National Fellowship, Department of Science and Technology (India).

Keywords

  • Apoptosis
  • Differentiation
  • HSP
  • NF-ΚB
  • TNF-α
  • αB-crystallin

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