Atencio I A, Ramachandra M, Shabram P, Demers G W
Canji, Inc., San Diego, California 92121, USA.
Cell Growth Differ. 2000 May;11(5):247-53.
Reports suggest a role of calpains in degradation of wild-type p53, which may regulate p53 induction of apoptosis. A calpain inhibitor, n-acetyl-leu-leu-norleucinal (calpain inhibitor 1), was assessed for ability to enhance p53-dependent apoptosis in human tumor cell lines with endogenous wild-type p53 and in altered p53 cell lines with the replacement of wild-type p53 by a recombinant adenovirus (rAd-p53). Calpain inhibitor 1 treatment resulted in increased levels of activated p53, increased p21 protein, and activation of caspases. Cell lines with wild-type, but not mutated or null, p53 status arrested in G0/G1 and were sensitive to calpain inhibitor-induced apoptosis. Regardless of endogenous p53 status, calpain inhibitor treatment combined with rAd-p53, but not empty vector virus, enhanced apoptosis in tumor cell lines. These results demonstrate p53-dependent apoptosis induced by a calpain inhibitor and further suggest a role for calpains in the regulation of p53 activity and induction of apoptotic pathways.
报告表明钙蛋白酶在野生型p53的降解中发挥作用，这可能调节p53诱导的细胞凋亡。评估了一种钙蛋白酶抑制剂N-乙酰-亮氨酰-亮氨酰-正亮氨酸（钙蛋白酶抑制剂1）增强具有内源性野生型p53的人肿瘤细胞系以及通过重组腺病毒（rAd-p53）取代野生型p53的p53改变细胞系中p53依赖性细胞凋亡的能力。钙蛋白酶抑制剂1处理导致活化p53水平升高、p21蛋白增加以及半胱天冬酶活化。具有野生型（而非突变型或缺失型）p53状态的细胞系停滞在G0/G1期，并且对钙蛋白酶抑制剂诱导的细胞凋亡敏感。无论内源性p53状态如何，钙蛋白酶抑制剂处理与rAd-p53联合使用（而非空载体病毒）可增强肿瘤细胞系中的细胞凋亡。这些结果证明了钙蛋白酶抑制剂诱导的p53依赖性细胞凋亡，并进一步表明钙蛋白酶在调节p53活性和诱导凋亡途径中发挥作用。
