Metallothionein and stress combine to affect multiple organ systems

Abstract

Metallothioneins (MTs) are a family of low molecular weight, cysteine-rich, metal-binding proteins that have a wide range of functions in cellular homeostasis and immunity. MTs can be induced by a variety of conditions including metals, glucocorticoids, endotoxin, acute phase cytokines, stress, and irradiation. In addition to their important immunomodulatory functions, MTs can protect essential cellular compartments from toxicants, serve as a reservoir of essential heavy metals, and regulate cellular redox potential. Many of the roles of MTs in the neuroinflammation, intestinal inflammation, and stress response have been investigated and were the subject of a session at the 6th International Congress on Stress Proteins in Biology and Medicine in Sheffield, UK. Like the rest of the cell stress response, there are therapeutic opportunities that arise from an understanding of MTs, and these proteins also provide potential insights into the world of the heat shock protein.

Fig. 1

The role of MTs in the formation of plaques in the brain. MTs have sex- and age-dependent effects on amyloidosis pathways throughout yet unknown mechanisms. At early ages, MTs seem to promote β-secretase activity directly (solid line) and eventually further processing of APP indirectly (dashed lines) and are thus detrimental. In contrast, at advanced ages, MTs decrease the amyloid cascade while promoting increased plaque formation (and concomitant microgliosis) and changing the Aβ_1–40:Aβ_1–42 ratios in cortex vs hippocampus in a sex-dependent manner

Fig. 2

Hypothetical scheme of stress-induced modulation of immunity. Biological, chemical, and physical/psychological stresses can independently or in combination increase oxidative stress leading to suppression of type 1 immunity, which is needed to defend against intracellular pathogens