Heparan-sulfate modulation of melatonin production in cultured pineal glands

Abstract

Heparan sulfate is a glycosaminoglycan of the extracellular matrix that is bound to a proteoglycan. When occur a disruption of matrix there is a formation of free disaccharides that could bind to toll-like receptors and trigger inflammatory responses. Knowing that the suppression of nocturnal melatonin production in the pineal gland is induced by molecular patterns associated to bacteria, fungi, and inflammatory cytokines are important to facilitate the assembly of an inflammatory response, in this project will be verified if free heparan sulfate could also lead to the suppression of melatonin production. The heparin sulfate effects on the activation of transcription factor NF-kB and the expression of genes encoding the inflammatory response, as well as the inhibition of the biosynthetic pathway and melatonin production will be evaluated in pineal in culture. We expect that heparan sulfate leads the pineal gland to a similar similar that is observed with LPS and induce the block of melatonin production. The demonstration that molecules from the extracellular matrix, and the damage signal to this matrix may alter the photic transduction to the whole organism is a new way of understanding pathophysiology bases dependent on desynchronization. (AU)