Physiologically relevant hCys concentrations mobilize MeHg from rabbit serum albumin to form MeHg-hCys complexes.

Abstract

Methylmercury (MeHg) is one of the most potent neurotoxins to which humans are exposed via the consumption of fish, from which it is effectively absorbed via the gastrointestinal tract into the bloodstream. Its interactions with plasma proteins, small-molecular-weight (SMW) molecules, and red blood cells, however, are incompletely understood, but critical as they determine whether and how much MeHg reaches target organs. To better define the role that SMW thiols play in the delivery of MeHg to known transporters located at the placental and blood-brain barrier, we have employed size exclusion chromatography-inductively coupled plasma-atomic emission spectroscopy to analyze MeHg-spiked rabbit plasma in the absence and presence of SMW thiols dissolved in the phosphate-buffered saline buffer mobile phase. While 300μM methionine did not affect the binding of MeHg to rabbit serum albumin (RSA), cysteine (Cys), homocysteine (hCys), and glutathione resulted in the elution of the main Hg peak in the SMW elution range. In addition, 50μM of hCys or Cys in the mobile phase resulted in the mobilization of MeHg from RSA in rabbit plasma and from pure RSA in solution. The Hg peak that eluted in the SMW elution range (50μM of hCys) was identified by electrospray ionization-mass spectrometry as an MeHg-hCys complex. Since l-type amino acid transporters are present at the blood-brain barrier (BBB), which facilitate the uptake of MeHg-Cys species into the brain, our results contribute to establish the bioinorganic mechanisms that deliver MeHg to the BBB, which is critical to predict organ-based adverse health effects.