Review article
https://doi.org/10.2478/aiht-2019-70-3317
Forgotten partners and function regulators of inducible metallothioneins
Mirela Pavić
orcid.org/0000-0003-4554-3247
; Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
Petra Turčić
orcid.org/0000-0002-2621-8257
; Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia
Marija Ljubojević
orcid.org/0000-0001-6333-2908
; Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia
Abstract
Metallothioneins are peculiar cysteine rich, heat resistant, small cellular plasma proteins expressed through almost all life forms. The currently established biological functions of metallothioneins are the homeostasis of essential metals and protection against toxic transitional metals (TM) alongside defence from oxidative stress by direct scavenging of reactive oxygen and nitrogen species (ROS and RNS). In mammals, among the four main evolutionary conserved forms, only the ubiquitously expressed metallothionein 1 and 2 (here abbreviated as MT) are inducible by TM, oxidative stress, glucocorticoids and starvation among various other stimuli. However, more than sixty years after being discovered, metallothioneins still bear unresolved issues about their possible physiological function and regulation. The biological function of MTs has still not been associated with the in vitro-demonstrated capacity of MT interaction with cellular molecules glutathione (GSH) or adenosine triphosphate (ATP), or with the possibility of direct iron-MT binding in the reducing intracellular environment of some organelles, e.g. lysosomes. Iron as the most abundant cellular TM is also one of the main physiological sources of ROS. Moreover, iron exhibits strain, sex and age differences that reflected ROS generation and MT induction in (patho)physiology and toxicology studies. A recent study showed that iron sex differences follows expression of both ferritin and MT leading to wide implications from essential TM interconnectivity to aging. This review places emphasis on biochemically proven but physiologically ignored interactions of MT with iron to stimulate advanced research for establishing a wide frame of the biological roles of MTs important for health and longevity.
Keywords
adenosine triphosphate; aging; copper; ferritin; glutathione; iron; oxidative stress; sex differences; steroid hormones; transition metals; zinc
Hrčak ID:
229297
URI
Publication date:
6.12.2019.
Visits: 1.186 *