Báo cáo khoa học: Modulation of nitric oxide-mediated metal release from metallothionein by the redox state of glutathione in vitro

Modulation of Nitric Oxide-Mediated Metal Release from Metallothionein by the Redox State of Glutathione In Vitro

Authors: Leila Khatai, Walter Goessler, Helena Lorencova, Klaus Zangger

Field: Biochemistry, Chemistry

Document Content: This study investigates the influence of glutathione’s redox state on the release of metals from metallothionein (MT) mediated by nitric oxide (NO) and peroxynitrite (ONOO⁻) in an in vitro setting. Metallothioneins are proteins known to bind heavy metals and play roles in detoxification and zinc homeostasis. Nitric oxide, particularly at inflammatory sites, is implicated in the release of metals from MTs, which in turn can suppress iNOS activity. The research explores how reduced glutathione (GSH) and oxidized glutathione (GSSG) affect this metal release mechanism. Using techniques such as CD spectroscopy, SEC-ICPMS, and NMR spectroscopy, the study found that GSH significantly suppresses NO- and ONOO⁻-mediated metal release from MT2, whereas GSSG does not exhibit this inhibitory effect. The findings suggest that under physiological conditions with millimolar concentrations of GSH in mammalian cells, NO-mediated metal release from MTs might not play a significant role in living systems. This observation points towards the involvement of other, yet unknown, mechanisms or compounds in in vivo interactions between NO and MTs. The research also highlights that zinc is released more readily than cadmium from MTs, and the release from the β-domain of MT-2 is comparable to that from the α-domain.

Detailed Table of Contents:

• Introduction
• Materials and Methods
• CD spectroscopy
• SEC-ICPMS
• NMR spectroscopy
• Results
• Discussion
• Acknowledgements
• References