Melatonin alleviates myosin light chain kinase expression and activity via the mitogen-activated protein kinase...

Area of Science:

• Biochemistry
• Cardiovascular Biology
• Pharmacology

Background:

• Melatonin (MLT), an endogenous indole compound, has demonstrated associations with atherosclerosis (AS).
• Myosin light chain kinase (MLCK) plays a role in endothelial cell function and its dysregulation is implicated in AS.
• The mitogen-activated protein kinase (MAPK) pathway is a key signaling cascade involved in cellular responses to various stimuli, including those relevant to AS.

Purpose of the Study:

• To investigate the effects of MLT on endothelial cell permeability, MLCK activity, and MLCK expression in an rabbit model of AS.
• To determine if MLT exerts its effects via the MAPK signaling pathway.
• To evaluate the therapeutic potential of MLT in reducing AS progression.

Main Methods:

• AS was induced in rabbits using a high-cholesterol diet.
• MLT treatment was administered to assess its impact on AS markers.
• MLCK activity and expression were quantified using western blot, qPCR, immunohistochemistry, and enzyme activity assays.
• Endothelial permeability was assessed via fluorescence staining.
• MAPK pathway activation (ERK, JNK, p38 phosphorylation) was analyzed using western blot.

Main Results:

• MLT treatment significantly reduced the number and area of atheromatous plaques in rabbits.
• MLT reversed the high-cholesterol-induced increase in MLCK activity and expression.
• MLT administration led to decreased phosphorylation of ERK, JNK, and p38 in endothelial cells.
• MLT treatment improved endothelial cell permeability.

Conclusions:

• Atherosclerosis is associated with increased MLCK expression and activity.
• MLT treatment effectively reduces AS progression by inhibiting MLCK.
• MLT's therapeutic effects are mediated, at least in part, through the modulation of the MAPK signaling pathway.