PMID- 33662875
OWN - NLM
STAT- MEDLINE
DCOM- 20210705
LR  - 20210705
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 41
DP  - 2021 May
TI  - Interactions of zinc- and redox-signaling pathways.
PG  - 101916
LID - S2213-2317(21)00064-1 [pii]
LID - 10.1016/j.redox.2021.101916 [doi]
LID - 101916
AB  - Zinc and cellular oxidants such as reactive oxygen species (ROS) each participate 
      in a multitude of physiological functions. There is considerable overlap between 
      the affected events, including signal transduction. While there is no obvious 
      direct connection between zinc and ROS, mainly because the bivalent cation zinc 
      does not change its oxidation state in biological systems, these are linked by 
      their interaction with sulfur, forming the remarkable triad of zinc, ROS, and 
      protein thiols. First, zinc binds to reduced thiols and can be released upon 
      oxidation. Thereby, redox signals are translated into changes in the free zinc 
      concentration, which can act as zinc signals. Second, zinc affects oxidation of 
      thiols in several ways, directly as well as indirectly. A protein incorporating 
      many of these interactions is metallothionein (MT), which is rich in cysteine and 
      capable of binding up to seven zinc ions in its fully reduced state. Zinc binding 
      is diminished after (partial) oxidation, while thiols show increased reactivity 
      in the absence of bound metal ions. Adding still more complexity, the MT promoter 
      is controlled by zinc (via metal regulatory transcription factor 1 (MTF-1)) as 
      well as redox (via nuclear factor erythroid 2-related factor 2 (NRF2)). Many 
      signaling cascades that are important for cell proliferation or apoptosis contain 
      protein thiols, acting as centers for crosstalk between zinc- and 
      redox-signaling. A prominent example for shared molecular targets for zinc and 
      ROS are active site cysteine thiols in protein tyrosine phosphatases (PTP), their 
      activity being downregulated by oxidation as well as zinc binding. Because zinc 
      binding also protects PTP thiols form irreversible oxidation, there is a 
      multi-faceted reciprocal interaction, illustrating that zinc- and redox-signaling 
      are intricately linked on multiple levels.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Hubner, Christopher
AU  - Hubner C
AD  - Technische Universitat Berlin, Chair of Food Chemistry and Toxicology, Strasse des 
      17. Juni 135, 10623, Berlin, Germany.
FAU - Haase, Hajo
AU  - Haase H
AD  - Technische Universitat Berlin, Chair of Food Chemistry and Toxicology, Strasse des 
      17. Juni 135, 10623, Berlin, Germany. Electronic address: haase@tu-berlin.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210224
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (Reactive Oxygen Species)
RN  - 9038-94-2 (Metallothionein)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - *Metallothionein
MH  - Oxidation-Reduction
MH  - Reactive Oxygen Species
MH  - Signal Transduction
MH  - *Zinc
PMC - PMC7937829
OTO - NOTNLM
OT  - Caspases
OT  - Metallothionein
OT  - Phosphatases
OT  - ROS
OT  - Redox metabolism
OT  - Zinc
EDAT- 2021/03/05 06:00
MHDA- 2021/07/06 06:00
PMCR- 2021/02/24
CRDT- 2021/03/04 20:20
PHST- 2021/01/17 00:00 [received]
PHST- 2021/02/19 00:00 [accepted]
PHST- 2021/03/05 06:00 [pubmed]
PHST- 2021/07/06 06:00 [medline]
PHST- 2021/03/04 20:20 [entrez]
PHST- 2021/02/24 00:00 [pmc-release]
AID - S2213-2317(21)00064-1 [pii]
AID - 101916 [pii]
AID - 10.1016/j.redox.2021.101916 [doi]
PST - ppublish
SO  - Redox Biol. 2021 May;41:101916. doi: 10.1016/j.redox.2021.101916. Epub 2021 Feb 
      24.