Melatonin signaling and cell protection function

Besides its well-known regulatory role on circadian rhythm, the pineal gland hormone melatonin has other biological functions and a distinct metabolism in various cell types and peripheral tissues. In different tissues and organs, melatonin has been described to act as a paracrine and also as an intracrine and autocrine agent with overall homeostatic functions and pleiotropic effects that include cell protection and prosurvival factor. These latter effects, documented in a number of in vitro and in vivo studies, are sustained through both receptor-dependent and -independent mechanisms that control detoxification and stress response genes, thus conferring protection against a number of xenobiotics and endobiotics produced by acute and chronic noxious stimuli. Redox-sensitive components are included in the cell protection signaling of melatonin and in the resulting transcriptional response that involves the control of NF-κB, AP-1, and Nrf2. By these pathways, melatonin stimulates the expression of antioxida...