Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation
2022
Аутори:
Zakić, TamaraStojanović, Sara
Janković, Aleksandra
Korać, Aleksandra
Peković‐Vaughan, Vanja
Korać, Bato
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2022 International Union of Biochemistry and Molecular Biology.
Метаподаци
Приказ свих података о документуАпстракт:
Adaptive responses to environmental and physiological challenges, including exposure to low environmental temperature, require extensive structural, redox, and metabolic reprogramming. Detailed molecular mechanisms of such processes in the skin are lacking, especially the role of nuclear factor erythroid 2-related factor 2 (Nrf2) and other closely related redox-sensitive transcription factors Nrf1, Nrf3, and nuclear respiratory factor (NRF1). To investigate the role of Nrf2, we examined redox and metabolic responses in the skin of wild-type (WT) mice and mice lacking functional Nrf2 (Nrf2 KO) at room (RT, 24 ± 1°C) and cold (4 ± 1°C) temperature. Our results demonstrate distinct expression profiles of major enzymes involved in antioxidant defense and key metabolic and mitochondrial pathways in the skin, depending on the functional Nrf2 and/or cold stimulus. Nrf2 KO mice at RT displayed profound alterations in redox, mitochondrial and metabolic responses, generally akin to cold-induced skin responses in WT mice. Immunohistochemical analyses of skin cell compartments (keratinocytes, fibroblasts, hair follicle, and sebaceous gland) and spatial locations (nucleus and cytoplasm) revealed synergistic interactions between members of the Nrf transcription factor family as part of redox-metabolic reprogramming in WT mice upon cold acclimation. In contrast, Nrf2 KO mice at RT showed loss of NRF1 expression and a compensatory activation of Nrf1/Nrf3, which was abolished upon cold, concomitant with blunted redox-metabolic responses. These data show for the first time a novel role for Nrf2 in skin physiology in response to low environmental temperature, with important implications in human connective tissue diseases with altered thermogenic responses.
Кључне речи:
cold; Nrf1; NRF1; Nrf2; Nrf3; redox-metabolic homeostasis; skinИзвор:
BioFactors, 2022Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200178 (Универзитет у Београду, Биолошки факултет) (RS-MESTD-inst-2020-200178)
- REFRAME - Exploring New Avenues in Breast Cancer Research: Redox and Metabolic Reprogramming of Cancer and Associated Adipose Tissue (RS-ScienceFundRS-Ideje-7750238)
- MRC-NIRG UK. Grant Number: MR/P003311/1
- MRC-Versus Arthritis UK as part of CIMA. Grant Numbers: MR/R502182/1, MR/P020941/1
- Rosetrees Trust. Grant Numbers: M709, CF-2021-2\133
- UKRI BBRSC. Grant Numbers: BB/W010801/1, BB/W018314/1
DOI: 10.1002/biof.1931
ISSN: 0951-6433
PubMed: 36585756
WoS: 000906094600001
Scopus: 2-s2.0-85145422798
URI
https://onlinelibrary.wiley.com/doi/10.1002/biof.1931http://radar.ibiss.bg.ac.rs/handle/123456789/5385