title: Effect of Transition Metals on Polysialic Acid Structure and Functions.
abstract: Polysialic acid (PSA) is one of the most abundant glycopolymer present in embryonic brain, and it is known to be involved in key roles such as plasticity in the central nervous system, cell adhesion, migration and localization of neurotrophins. However, in adult brain, its expression is quite low. The exception to this is in Alzheimer's disease (AD) brain, where significantly increased levels of polysilylated neural cell adhesion molecule (PSA-NCAM) have been reported. Here, we confirm the role of PSA as a metal chelator, allowing it to decrease cytotoxicity caused by high levels of transition metals, commonly found in AD brain, and as a regulator of cell behavior. UV-visible (UV-vis) and circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), and isothermal titration calorimetry (ITC) techniques were used to investigate the assembly of PSA-metals complexes. These PSA-metal complexes exhibited less toxicity compared to free metal ions, and in particular, the PSA-Cu(2+) complex synergistically promoted neurite outgrowth in PC12 cells.
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, 411021, India.
authors.forename: Raghavendra Vasudeva
authors.initials: RV
authors.lastname: Murthy
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, 411021, India.
authors.forename: Priya
authors.initials: P
authors.lastname: Bharate
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, 411021, India.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Gade
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, 411021, India.
authors.forename: Sivakoti
authors.initials: S
authors.lastname: Sangabathuni
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, 411021, India. rkikkeri@iiserpune.ac.in.
authors.forename: Raghavendra
authors.identifier: http://orcid.org/0000-0002-4451-6338
authors.initials: R
authors.lastname: Kikkeri
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D016501:Neurites / Q000187:drug effects; D000071446:Neuronal Outgrowth / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D012794:Sialic Acids / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D028561:Transition Elements / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D002614:Chelating Agents; D012794:Sialic Acids; D028561:Transition Elements; C021319:polysialic acid; D003300:Copper
keywords: kinases; neural cell differentiation; polysialic acid; toxicity; transition metals