Effect of Calpain on The Degradation of Tau in Rat Brain Co rtex Extracts

Calpain is a calcium-activated protease and there are two u biquitously distributed mammalian calpains, namely calpain 1 (μ-calpain and CAPN1) and calpain 2 (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 brain cortex extracts were incubated with 0 2 mmol/L, 1 mmol/L, 3 mmol/L and 5 mmol/L of CaCl 2 for 15 min at 37℃. The findings were that Ca 2+ treatment at concentration 1～5 mmol/L led to significant proteolysis of tau protein and this degradation was blocked by calpain inhibitor, calpeptin. In addition, when the extracts containing 1 mmol/L CaCl 2 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 Ca 2+ -induced degradation of tau protein was decreased to 8 6%,92 5% and 97 8%, respectively. These data suggest that both μ-calpain and m-calpain in brain cortex extracts are activated by Ca 2+ and both of them degrade tau protein, although, m-calpain plays a more important role in proteolysis of tau.