Modulation of rat pineal gland melatonin synthesis by heparan sulfate.

Author(s)

Michelle Acco Gomes

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2016-03-22

Examining board members

Regina Pekelmann Markus; Carolina Demarchi Munhoz; Ivarne Luis dos Santos Tersariol

• Advisor: Regina Pekelmann Markus

Abstract

The nocturnal synthesis of melatonin by the pineal gland is inhibited by pathogen or damage-associated molecular patterns, such as lipopolysaccharide (LPS) and β-amyloid peptide. The interaction of these molecules with toll like receptors 4 (TLR4) activates the immune-pineal axis, favoring the migration of leukocytes for the site of lesion. Heparan sulfate (HS), a glycosaminoglycan of the extracellular matrix, that in case of tissue injury, generalized inflammation or migration of tumor cells, releases disaccharide, which can bind to TLR4 triggering an inflammatory response. Here we evaluated if HS could impair nocturnal melatonin activity. HS is capable of inhibit the melatonin synthesis by the suppression of the gene expression and enzymatic content of acetylserotonin O-methyltransferase (ASMT). This effect is modulated by the interaction of HS with TLR4, but does not involve the NF-κB nuclear translocation pathway. This data suggest that the increase in HS in pineal gland matrix is translated to the whole organism by a reduction in the nocturnal melatonin peak. (AU)

• FAPESP's process: 13/15037-7 - Heparan-sulfate modulation of melatonin production in cultured pineal glands
• Grantee: Michelle Acco Gomes
• Support Opportunities: Scholarships in Brazil - Master