An Interplay of S-Nitrosylation and Metal Ion Binding for Astrocytic S100B Protein

PLoS One. 2016 May 9;11(5):e0154822. doi: 10.1371/journal.pone.0154822. eCollection 2016.

Abstract

Mammalian S100B protein plays multiple important roles in cellular brain processes. The protein is a clinically used marker for several pathologies including brain injury, neurodegeneration and cancer. High levels of S100B released by astrocytes in Down syndrome patients are responsible for reduced neurogenesis of neural progenitor cells and induction of cell death in neurons. Despite increasing understanding of S100B biology, there are still many questions concerning the detailed molecular mechanisms that determine specific activities of S100B. Elevated overexpression of S100B protein is often synchronized with increased nitric oxide-related activity. In this work we show S100B is a target of exogenous S-nitrosylation in rat brain protein lysate and identify endogenous S-nitrosylation of S100B in a cellular model of astrocytes. Biochemical studies are presented indicating S-nitrosylation tunes the conformation of S100B and modulates its Ca2+ and Zn2+ binding properties. Our in vitro results suggest that the possibility of endogenous S-nitrosylation should be taken into account in the further studies of in vivo S100B protein activity, especially under conditions of increased NO-related activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Astrocytes / metabolism*
  • Calorimetry
  • Cell Line, Tumor
  • Male
  • Mass Spectrometry
  • Metals / metabolism*
  • Nitroso Compounds / metabolism*
  • Osmolar Concentration
  • Protein Binding
  • Rats
  • Rats, Wistar
  • S100 Calcium Binding Protein beta Subunit / chemistry
  • S100 Calcium Binding Protein beta Subunit / metabolism*
  • Sequence Homology, Amino Acid

Substances

  • Metals
  • Nitroso Compounds
  • S100 Calcium Binding Protein beta Subunit

Grant support

This study was supported by grants from Polish Ministry of Science and Higher Education (2543/B/P01/2007/33; http://www.nauka.gov.pl/en/) to AWC and National Center for Research and Development (POIG.01.01.02-00-048/09; http://www.ncbr.gov.pl/en/) to AWC.