High glucose upregulates myosin light chain kinase to induce microfilament cytoskeleton rearrangement in hippocampal neurons

Abstract

Chronic hyperglycemia leads to myosin light chain kinase (MLCK) upregulation and induces neuronal damage. However, the underlying molecular mechanism of neuronal damage in hyperglycemia has not yet been fully elucidated. In the present study, hippocampal neuronal cells were cultured and treated with a high glucose concentration (45 mmol/l). The results demonstrated that high glucose induced shrinking of the synapses, nuclear shape irregularity and microfilament damage. Filamentous actin (F-actin) filaments were rearranged, cell apoptosis rate was increased and the protein expression of MLCK and phosphorylated (p)-MLC was upregulated. The MLCK inhibitor ML-7 largely reversed the alterations in the microfilament cytoskeleton, inhibited F-actin depolymerization, reduced apoptosis and downregulated MLCK and p-MLC protein expression. Overall, these results indicated that high glucose upregulated MLCK to promote F-actin depolymerization, which induced microfilament cytoskeleton rearrangement in hippocampal neuronal cells.

Low intensity pulsed ultrasound promotes the migration of bone marrow- derived mesenchymal stem cells via activating FAK-ERK1/2 signalling pathway

“…ERK1/2 has been shown to phosphorylate myosin light chain kinase (MLCK), which phosphorylates myosin light chain (MLC) at Thr18/Ser19 and thereby stimulates MLC activity [37,38]. Activated MLC promoted microfilament contraction and accelerates cell migration [39]. In this study, FAK and ERK1/2 activated LIPUS enhanced MLC activation, thereby facilitating cell migration, and that this process was inhibited by specific FAK inhibitor (PF-773228) and ERK inhibitor (U0126), the amounts of phospho-FAK, phospho-ERK1/2, phospho-MLC significantly decreased, which was highly possible that LIPUS promotes the BMSCs migration via the phosphorylation and activation of FAK-ERK signalling pathway.…”

Green tea protects against hippocampal neuronal apoptosis in diabetic encephalopathy by inhibiting JNK/MLCK signaling

“…Green tea protects against hippocampal neuronal apoptosis via the JNK/MLCK pathway. The JNK signaling pathway serves an important role in apoptosis and our previous study found that MLCK serves a role in hippocampal neuronal apoptosis in DE (14). Therefore, the present study further examined the relationship between the JNK pathway and MLCK.…”

“…Hippocampal neuronal cell culture and identification. The primary hippocampal neurons were cultured according to a previously published method (14). Newborn SD rat were sacrificed by cervical dislocation and the mortality of the animals confirmed by cessation of heartbeat.…”

“…In addition, increased MLCK expression affects the cytoskeletal structure and this effect leads to the occurrence of apoptosis (12). Our previous studies found that MLCK serves a role in hippocampal neuronal apoptosis, but the regulatory mechanism Green tea protects against hippocampal neuronal apoptosis in diabetic encephalopathy by inhibiting JNK/MLCK signaling needs further examination (13,14). Previous research has shown that hippocampal neuronal apoptosis is regulated by multiple pathways, including the MAPK/JNK signaling pathway and the Wnt/β-catenin signaling pathway (15).…”

Study on the solitary wave solutions of the ionic currents on microtubules equation by using the modified Khater method

“…Li Marc Kirschner and Tim Mitchison suggested in (1986s) that, the microtubules can employ its dynamic characteristics of growth and contraction at their plus ends to probe the 3-D space of the cell. In contrary to regular dynamism microtubules, that has a half-life of 5-10 minutes [11][12][13][14][15]. Electrostatics of nanosystems is considered as one of the applications of the microtubules.…”