Forgotten partners and function regulators of inducible metallothioneins

Scientific paper - Review paper

• Title (croatian): Zaboravljeni partneri i regulatori funkcije inducibilnih metalotioneina
• Author: Mirela Pavić https://orcid.org/0000-0003-4554-3247
• Author: Petra Turčić
• Author: Marija Ljubojević https://orcid.org/0000-0001-6333-2908
• Author's institution: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract (english)

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.

Abstract (croatian)

Metalotioneini su mali proteini stanične plazme specifični po zastupljenosti cisteina i otpornosti na toplinu, a izraženi su kroz gotovo sve oblike života. U sisavaca, među četirima glavnim evolucijski očuvanim oblicima, samo se sveprisutno izraženi metalotioneini 1 i 2 (u daljnjem tekstu MT) induciraju s različitim prijelaznim metalima (TM), oksidacijskim stresom, glukokortikoidima, gladovanjem između ostalih stimulansa. Trenutna uspostavljena uloga MT-ova u stanici je homeostaza esencijalnih i zaštita od toksičnih TM-ova, zajedno s obranom od oksidacijskoga stresa izravnim uklanjanjem reaktivnih kisikovih i dušikovih vrsta (ROS/RNS). Međutim, čak i više od šezdeset godina nakon otkrića, oko metalotioneina i dalje postoje neka neriješena pitanja o njihovoj funkciji i regulaciji. Naime, funkcija MT-ova još uvijek nije povezana s in vitro dokazanom sposobnošću vezanja MT-ova sa staničnim molekulama GSH-a ili ATP-a, zajedno s važnim procesom vezanja željeza MT-a u reduktivnom okolišu npr. lizosoma. Željezo kao najzastupljeniji stanični TM također je i glavni izvor ROS-a. Ujedno željezo pokazuje razlike između vrsta i sojeva te među spolovima i u starenju, koje mogu odražavati nastajanje ROS-ova i izražaj MT-ova u (pato)fiziološkim i toksikološkim istraživanjima. Promjene MT-ova koje prate razlike u željezu nedavno su dokazane i imaju široke implikacije od međusobne povezanosti esencijalnih TM-ova do starenja. Ovaj pregledni članak stavlja naglasak na biokemijski dokazane ali većinom fiziološki ignorirane interakcije in vitro MT-ova i željeza za poticaj naprednih istraživanja koja bi izgradila širu mrežu MT-ove biološke uloge važne za zdravlje i dugovječnost.

• Keywords (english): adenosine triphosphate; aging; copper; ferritin; glutathione; iron; oxidative stress; sex differences; steroid hormones; transition metals; zinc
• Keywords (croatian): adenozintrifosfat; bakar; cink; feritin; glutation; oksidacijski stres; prijelazni metali; spolne razlike; starenje; steroidni hormoni; željezo
• Language: english
• Language: croatian
• Publication type: Scientific paper - Review paper
• Publication status: Published
• Peer review: Peer review - international
• Publication version: Published version
• Journal title: Arhiv za higijenu rada i toksikologiju
• Numbering: vol. 70, no. 4, pp. 256-263
• p-ISSN: 0004-1254
• e-ISSN: 1848-6312
• DOI: https://doi.org/10.2478/aiht-2019-70-3317
• URN:NBN: urn:nbn:hr:163:910358
• Publication: 2019
• Document URL: https://hrcak.srce.hr/229297
• Type of resource: Text
• Access conditions: Open access
• Created on: 2020-05-14 11:55:12