HOX-1 and COX-2: Two differentially regulated key mediators of skeletal myoblast tolerance under oxidative stress

Abstract

The exact physiological role of oxidative stress as a primary cause for skeletal muscle pathological conditions involving muscle degeneration remains elusive. Therefore, the present study was performed so as to decipher the signalling pathways orchestrating the potential cytoprotective role of heme oxygenase 1 (HOX-1) as well as cyclooxygenase 2 (COX-2) in skeletal myoblasts exposed to H₂O₂. Cell treatment with H₂O₂ (0.5 mM) resulted in a time- and dose-dependent response of HOX-1 and COX-2 mRNA and protein levels, with ERK1/2, p38-MAPK and MSK1 found to mediate these effects. Furthermore, Src and JNKs blockade attenuated COX-2 response. Collectively, these novel findings highlight for the first time HOX-1 and COX-2 fundamental contribution to skeletal myoblast tolerance under oxidative stress, since their inhibition significantly attenuated viability of skeletal myoblasts. The data also delineate the various effectors regulating HOX-1 and COX-2 expression, probably alleviating muscle degeneration in related disorders.

Keywords::

• HOX-1
• COX-2
• protein kinases
• survival
• skeletal myoblast
• hydrogen peroxide

Declaration of interest: This work was funded by grants of the Special Research Account of the University of Athens. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This paper was first published online on Early Online on 07 April 2010.