[Effect of calpain on the degradation of tau protein in rat brain cortex extracts].
Calpain is a calcium-activated protease and has two ubiquitously distributed mammalian isoforms, namely calpain 1 (calpain I, mu-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 CaCl(2 )for 15 min at 37 degrees C, respectively, and it was found that Ca(2+) 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 CaCl(2 )were treated with mu-calpain inhibitor (0.05 micromol/L of calpastatin) or m-calpain inhibitor (100 micromol/L calpain inhibitor IV) or both, the Ca(2+)-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 mu-calpain and m-calpain in brain cortex extracts are activated by Ca(2+) and both of them degraded tau protein, although, m-calpain plays a more important role in proteolysis of the tau protein.
Fang
Zheng-Yu
ZY
Neuroscience Institute Pathophysiology Department Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China.
Liu
Shi-Jie
SJ
Wang
Xiao-Chuan
XC
Liu
Rong
R
Wang
Qun
Q
Chen
Zheng-Yue
ZY
Wang
Jian-Zhi
JZ
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002154:Calpain / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; D002154:Calpain; D002122:Calcium Chloride