Matrix metalloproteinases in health and disease: Regulation by melatonin

Matrix metalloproteinases (MMPs) are part of a superfamily of metal-requiring proteases that play important roles in tissue remodeling by breaking down proteins in the extracellular matrix that provides structural support for cells. The intricate balance in protease/anti-protease stoichiometry is a contributing factor in a number of diseases. Melatonin possesses multifunctional bioactivities including antioxidative, anti-inflammatory, endocrinologic and behavioral effects. As melatonin affects the redox status of tissues, the association of reactive oxygen species (ROS) with tissue injury under different circumstances may be mitigated by melatonin. Redox signaling is expanding into all areas of basic and clinical sciences, and this timely review focuses on the topic of regulation of MMP activities by melatonin. This is a rapidly growing field. Accumulating evidence indicates that oxidative stress plays an important role in regulating the activities of MMPs that are involved in various cellular processes such as cellular proliferation, angiogenesis, apoptosis, invasion and metastasis. This review offers sections on MMPs, melatonin, major physiological and pathophysiological conditions in the context to MMPs, followed by redox signaling mechanisms that are known to influence the cellular processes. Finally, we discuss the emerging molecular mechanisms relevant to regulatory actions of melatonin on the activities of MMPs. The possibility that melatonin might have therapeutic significance via regulation of MMPs may be a novel approach in the treatment of some diseases.