Role of the small Hsp αBcrystallin in protecting skeletal myoblasts from cell death induced by oxidative stress

αB-crystallin, a member of the small heat shock protein (HSP)1 family, highly expressed in the lens, has chaperone-like anti-aggregation properties and is also present in skeletal and cardiac muscle, skin, brain and kidney. aB-crystallin stabilizes and protects target proteins including desmin and is involved in the cellular defence against various forms of stress. It is selectively induced in C2C12 myoblasts that are resistant to differentiation-induced apoptosis, and it negatively regulates apoptosis during myogenesis by inhibiting the proteolytic activation of caspase-3. We analysed the involvement of αB-crystallin in the adaptive response towards oxidative stress induced in L6C5 and C2C12 myoblasts either by Reactive Oxygen Species or by VEGF, both induced during the contraction of muscle fibers. After treatment with low concentrations of H2O2, L6C5 myoblasts became more resistant to the induction of apoptosis and chromosomal aberrations determined by the exposure to high H2O2 concentrations. We verified that this adaptive response was correlated to the increase of aB-crystallin, the increase of the apurinic/apyrimidinic endonuclease APE 1, involved in repairing the DNA damage caused by oxidative stress and regulating the redox state of different transcription factors, and of Bcl-2. The over-expression of the anti apoptotic protein αB-crystallin is also correlated to the protection from ROS-induced apoptosis exerted by VEGF in C2C12 myoblasts. In this case, the protection, clearly linked to the phosphorylation of KDR/Flk-1 receptor and the activation of NFkB transcription factor, seems specifically dependent from the increase of αB-crystallin concentration, being not paralleled by modulation of the anti-apoptotic proteins, such as Bcl-2 or Bcl-xL, but almost completely abrogated after downregulation of αB-crystallin protein trough siRNAs silencing.