Cleavage of calnexin caused by apoptotic stimuli: Implication for the regulation of apoptosis

金沢大学医薬保健研究域薬学系Calnexin is an endoplasmic reticulum (ER)-resident molecular chaperone that plays an essential role in the correct folding of membrane proteins. We found that calnexin is subjected to partial cleavage in apoptotic mouse cells. Both ER stress-inducing and ER stress-non-inducing apoptotic stimuli caused the cleavage of calnexin, indicating that this event does not always occur downstream of ER stress. The inhibition of caspases that target the amino acid sequence DXXD abrogated calnexin cleavage in apoptotic stimulus-treated cells. In addition, disruption of one of two DXXD sequences located in the cytoplasmic domain caused calnexin to escape cleavage during apoptosis. Furthermore, calnexin was cleaved in vitro by recombinant caspase-3 or caspase-7. Finally, the overexpression of a presumed cleavage product of calnexin partly inhibited apoptosis. These results collectively suggest that caspase-3 or caspase-7 cleaves calnexin, whose cleaved product leads to the attenuation of apoptosis

Pathological changes in levels of three small stress proteins, αB crystallin, HSP 27 and P20, in the hindlimb muscles of dy mouse

AbstractUsing three different analyses, we investigated the levels of the three small stress proteins αB crystallin, HSP 27 and p20 in the slow-twitch soleus muscle and fast-twitch tibialis anterior muscle of normal and dy mice. All of these analyses (immunoassay, Western blot and immunohistochemistry) showed markedly increased levels of these stress proteins in fast-twitch type muscle (tibialis anterior muscle) of dy mouse. In contrast, the levels of αB crystallin, HSP 27 and p20 of dy mouse were reduced in slow-twitch type muscle (soleus muscle). Manipulation of this protective response may reduce injury and may have potential therapeutic application in congenital muscular dystrophy (CMD), which possesses a deficiency of laminin-α2 chain in muscle fiber basement similar to dy mouse