Calpain-2 activity promotes aberrant endoplasmic reticulum stress-related apoptosis in hepatocytes
Rujia Xie, Xiaoxia Hu, Lu Zheng, Shuang Cai, Yusi Chen, Yi Yang, Ting Yang, Bing Han, Qin Yang
Abstract
BACKGROUND: -dependent cysteine protease, and high calpain-2 activity can enhance apoptosis mediated by multiple triggers. AIM: To investigate whether calpain-2 can modulate aberrant endoplasmic reticulum (ER) stress-related apoptosis in rat hepatocyte BRL-3A cells. METHODS: content, and ER and calpain-2 co-localization were characterized by fluorescent microscopy. The impact of calpain-2 silencing by specific small interfering RNA on caspase-12 activation and apoptosis of BRL-3A cells was quantified. RESULTS: content, calpain-2 expression, and activity by >2-fold in BRL-3A cells. Furthermore, immunofluorescence revealed that DTT treatment promoted the ER accumulation of calpain-2. Moreover, calpain-2 silencing to decrease calpain-2 expression by 85% significantly mitigated DTT-enhanced calpain-2 expression, caspase-12 cleavage, and apoptosis in BRL-3A cells. CONCLUSION: -dependent calpain-2 activity promoted the aberrant ER stress-related apoptosis of rat hepatocytes by activating caspase-12 in the ER.