Calpain is a calcium-activated protease and has two ubiquitously distributed mammalian isoforms, namely calpain 1 (calpain I, μ-calpain and CAPN1) and calpain 2 (calpain II, m-calpain and CAPN2). Calpains regulate the function of many proteins by limited proteolysis. To determine the nature of different subtypes of calpain on degradation of microtubule-associated protein tau, the rat cortex extracts were incubated with 0.2 mmol/L, 1 mmol/L, 3 mmol/L and 5 mmol/L of CaCl2 for 15 min at 37°C, respectively, and it was found that Ca2+ treatment at concentrations 1-5 mmol/L led to significant proteolysis of the tau protein and this degradation was blocked by calpain inhibitor, calpeptin. In addition, when the extracts containing 1 mmol/ L CaCl2 were treated with μ-calpain inhibitor (0.05 μmol/L of calpastatin) or m-calpain inhibitor (100 μmol/L calpain inhibitor IV) or both, the Ca2+-induced degradation of tau protein was blocked to about 8.6%, 92.5% and 97.8% compared with the group with 1 mmol/L CaCl 2, respectively. These data suggest that both μ-calpain and m-calpain in brain cortex extracts are activated by Ca2+ and both of them degraded tau protein, although, m-calpain plays a more important role in proteolysis of the tau protein.
|Number of pages||6|
|Journal||Acta Biochimica et Biophysica Sinica|
|Publication status||Published - 22 Aug 2003|
- Alzheimer disease
- Tau protein