Calpain-2 plays a pivotal role in the inhibitory effects of propofol against TNF- α-induced autophagy in mouse hippocampal neurons.

Calpain-2 plays a pivotal role in the inhibitory effects of propofol against TNF-α-induced autophagy in mouse hippocampal neurons.
J Cell Mol Med. 2020 Jul 06;:
Authors: Li Y, He Z, Lv H, Chen W, Chen J
Abstract
Calpains are calcium-dependent proteases and play critical roles in neuronal autophagy induced by inflammation. Propofol has been reported to exert anti-inflammatory effects in neurons. We aimed to identify whether and how propofol-modulated calpain activity and neuron autophagy in response to tumour necrosis factor-α (TNF-α). Mouse hippocampal neurons were pre-treated with propofol and exposed to TNF-α. Autophagy was evaluated by fluorescent autophagy assay and by measuring LC3I and LC3II expression. Intracellular calcium concentration was measured by fluorescent assay. Calpain activation was measured by calpain activity assay. The protein expression of intracellular signalling molecules was detected by Western blot analysis. Compared with untreated control neurons, 40 ng/mL TNF-α treatment for 2 hours induced neuron autophagy, which was attenuated by 25 μmol/L propofol. TNF-α induced intracellular calcium accumulation, the phosphorylation of calcium/calmodulin-dependent protein kinase II (CAMK II) and calpain-2, calpain activation and lysosomal cathepsin B release as well as tyrosine kinase receptor B (TrkB) truncation. These effects were alleviated by propofol, calcium chelator, CAMK II inhibitor, calpain-2 inhi...

Source: J Cell Mol Med - July 5, 2020 Category: Molecular Biology Authors: Li Y, He Z, Lv H, Chen W, Chen J Tags: J Cell Mol Med Source Type: research