Oxidative Damage Control in a Human (Mini-) Organ: Nrf2 Activation Protects against Oxidative Stress-Induced Hair Growth Inhibition

Iain S. Haslam, Laura Jadkauskaite, Imre Lőrinc Szabó, Selma Staege, Jasper Hesebeck-brinckmann, Gail Jenkins, Ranjit K. Bhogal, Fei-ling Lim, Nilofer Farjo, Bessam Farjo, Tamás Bíró, Matthias Schäfer, Ralf Paus

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Abstract

The in situ control of redox insult in human organs is of major clinical relevance, yet remains incompletely understood. Activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the “master regulator” of genes controlling cellular redox homeostasis, is advocated as a therapeutic strategy for diseases with severely impaired redox balance. It remains to be shown whether this strategy is effective in human organs, rather than only in isolated human cell types. We have therefore explored the role of Nrf2 in a uniquely accessible human (mini-) organ: scalp hair follicles. Microarray and qRT-PCR analysis of human hair follicles after Nrf2 activation using sulforaphane identified the modulation of phase II metabolism, reactive oxygen species clearance, the pentose phosphate pathway, and glutathione homeostasis. Nrf2 knockdown (small interfering RNA) in cultured human hair follicles confirmed the regulation of key Nrf2 target genes (i.e., heme oxygenase-1, NAD(P)H dehydrogenase, quinone 1, glutathione reductase, glutamate-cysteine ligase catalytic subunit, ABCC1, peroxiredoxin 1). Importantly, Nrf2 activation significantly reduced reactive oxygen species levels and associated lipid peroxidation. Nrf2 preactivation reduced premature catagen and hair growth inhibition induced by oxidative stress (H2O2 or menadione), significantly ameliorated the H2O2-dependent increase in matrix keratinocyte apoptosis and reversed the reactive oxygen species-induced reduction in hair matrix proliferation. This study thus provides direct evidence for the crucial role of Nrf2 in protecting human organ function (i.e., scalp hair follicles) against redox insult.
LanguageEnglish
Pages295-304
Number of pages10
JournalJournal of Investigative Dermatology
Volume137
Issue number2
Early online date1 Oct 2016
DOIs
Publication statusPublished - Feb 2017

Fingerprint

Oxidative stress
Hair
Oxidative Stress
Chemical activation
Hair Follicle
Reactive Oxygen Species
Growth
Oxidation-Reduction
Genes
Glutamate-Cysteine Ligase
NAD(P)H Dehydrogenase (Quinone)
Peroxiredoxins
Pentoses
Vitamin K 3
Heme Oxygenase-1
Glutathione Reductase
Scalp
Microarrays
Metabolism
Small Interfering RNA

Cite this

Haslam, Iain S. ; Jadkauskaite, Laura ; Szabó, Imre Lőrinc ; Staege, Selma ; Hesebeck-brinckmann, Jasper ; Jenkins, Gail ; Bhogal, Ranjit K. ; Lim, Fei-ling ; Farjo, Nilofer ; Farjo, Bessam ; Bíró, Tamás ; Schäfer, Matthias ; Paus, Ralf. / Oxidative Damage Control in a Human (Mini-) Organ : Nrf2 Activation Protects against Oxidative Stress-Induced Hair Growth Inhibition. In: Journal of Investigative Dermatology. 2017 ; Vol. 137, No. 2. pp. 295-304.
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title = "Oxidative Damage Control in a Human (Mini-) Organ: Nrf2 Activation Protects against Oxidative Stress-Induced Hair Growth Inhibition",
abstract = "The in situ control of redox insult in human organs is of major clinical relevance, yet remains incompletely understood. Activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the “master regulator” of genes controlling cellular redox homeostasis, is advocated as a therapeutic strategy for diseases with severely impaired redox balance. It remains to be shown whether this strategy is effective in human organs, rather than only in isolated human cell types. We have therefore explored the role of Nrf2 in a uniquely accessible human (mini-) organ: scalp hair follicles. Microarray and qRT-PCR analysis of human hair follicles after Nrf2 activation using sulforaphane identified the modulation of phase II metabolism, reactive oxygen species clearance, the pentose phosphate pathway, and glutathione homeostasis. Nrf2 knockdown (small interfering RNA) in cultured human hair follicles confirmed the regulation of key Nrf2 target genes (i.e., heme oxygenase-1, NAD(P)H dehydrogenase, quinone 1, glutathione reductase, glutamate-cysteine ligase catalytic subunit, ABCC1, peroxiredoxin 1). Importantly, Nrf2 activation significantly reduced reactive oxygen species levels and associated lipid peroxidation. Nrf2 preactivation reduced premature catagen and hair growth inhibition induced by oxidative stress (H2O2 or menadione), significantly ameliorated the H2O2-dependent increase in matrix keratinocyte apoptosis and reversed the reactive oxygen species-induced reduction in hair matrix proliferation. This study thus provides direct evidence for the crucial role of Nrf2 in protecting human organ function (i.e., scalp hair follicles) against redox insult.",
author = "Haslam, {Iain S.} and Laura Jadkauskaite and Szab{\'o}, {Imre Lőrinc} and Selma Staege and Jasper Hesebeck-brinckmann and Gail Jenkins and Bhogal, {Ranjit K.} and Fei-ling Lim and Nilofer Farjo and Bessam Farjo and Tam{\'a}s B{\'i}r{\'o} and Matthias Sch{\"a}fer and Ralf Paus",
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Haslam, IS, Jadkauskaite, L, Szabó, IL, Staege, S, Hesebeck-brinckmann, J, Jenkins, G, Bhogal, RK, Lim, F, Farjo, N, Farjo, B, Bíró, T, Schäfer, M & Paus, R 2017, 'Oxidative Damage Control in a Human (Mini-) Organ: Nrf2 Activation Protects against Oxidative Stress-Induced Hair Growth Inhibition', Journal of Investigative Dermatology, vol. 137, no. 2, pp. 295-304. https://doi.org/10.1016/j.jid.2016.08.035

Oxidative Damage Control in a Human (Mini-) Organ : Nrf2 Activation Protects against Oxidative Stress-Induced Hair Growth Inhibition. / Haslam, Iain S.; Jadkauskaite, Laura; Szabó, Imre Lőrinc; Staege, Selma; Hesebeck-brinckmann, Jasper; Jenkins, Gail; Bhogal, Ranjit K.; Lim, Fei-ling; Farjo, Nilofer; Farjo, Bessam; Bíró, Tamás; Schäfer, Matthias; Paus, Ralf.

In: Journal of Investigative Dermatology, Vol. 137, No. 2, 02.2017, p. 295-304.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Oxidative Damage Control in a Human (Mini-) Organ

T2 - Journal of Investigative Dermatology

AU - Haslam, Iain S.

AU - Jadkauskaite, Laura

AU - Szabó, Imre Lőrinc

AU - Staege, Selma

AU - Hesebeck-brinckmann, Jasper

AU - Jenkins, Gail

AU - Bhogal, Ranjit K.

AU - Lim, Fei-ling

AU - Farjo, Nilofer

AU - Farjo, Bessam

AU - Bíró, Tamás

AU - Schäfer, Matthias

AU - Paus, Ralf

PY - 2017/2

Y1 - 2017/2

N2 - The in situ control of redox insult in human organs is of major clinical relevance, yet remains incompletely understood. Activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the “master regulator” of genes controlling cellular redox homeostasis, is advocated as a therapeutic strategy for diseases with severely impaired redox balance. It remains to be shown whether this strategy is effective in human organs, rather than only in isolated human cell types. We have therefore explored the role of Nrf2 in a uniquely accessible human (mini-) organ: scalp hair follicles. Microarray and qRT-PCR analysis of human hair follicles after Nrf2 activation using sulforaphane identified the modulation of phase II metabolism, reactive oxygen species clearance, the pentose phosphate pathway, and glutathione homeostasis. Nrf2 knockdown (small interfering RNA) in cultured human hair follicles confirmed the regulation of key Nrf2 target genes (i.e., heme oxygenase-1, NAD(P)H dehydrogenase, quinone 1, glutathione reductase, glutamate-cysteine ligase catalytic subunit, ABCC1, peroxiredoxin 1). Importantly, Nrf2 activation significantly reduced reactive oxygen species levels and associated lipid peroxidation. Nrf2 preactivation reduced premature catagen and hair growth inhibition induced by oxidative stress (H2O2 or menadione), significantly ameliorated the H2O2-dependent increase in matrix keratinocyte apoptosis and reversed the reactive oxygen species-induced reduction in hair matrix proliferation. This study thus provides direct evidence for the crucial role of Nrf2 in protecting human organ function (i.e., scalp hair follicles) against redox insult.

AB - The in situ control of redox insult in human organs is of major clinical relevance, yet remains incompletely understood. Activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the “master regulator” of genes controlling cellular redox homeostasis, is advocated as a therapeutic strategy for diseases with severely impaired redox balance. It remains to be shown whether this strategy is effective in human organs, rather than only in isolated human cell types. We have therefore explored the role of Nrf2 in a uniquely accessible human (mini-) organ: scalp hair follicles. Microarray and qRT-PCR analysis of human hair follicles after Nrf2 activation using sulforaphane identified the modulation of phase II metabolism, reactive oxygen species clearance, the pentose phosphate pathway, and glutathione homeostasis. Nrf2 knockdown (small interfering RNA) in cultured human hair follicles confirmed the regulation of key Nrf2 target genes (i.e., heme oxygenase-1, NAD(P)H dehydrogenase, quinone 1, glutathione reductase, glutamate-cysteine ligase catalytic subunit, ABCC1, peroxiredoxin 1). Importantly, Nrf2 activation significantly reduced reactive oxygen species levels and associated lipid peroxidation. Nrf2 preactivation reduced premature catagen and hair growth inhibition induced by oxidative stress (H2O2 or menadione), significantly ameliorated the H2O2-dependent increase in matrix keratinocyte apoptosis and reversed the reactive oxygen species-induced reduction in hair matrix proliferation. This study thus provides direct evidence for the crucial role of Nrf2 in protecting human organ function (i.e., scalp hair follicles) against redox insult.

U2 - 10.1016/j.jid.2016.08.035

DO - 10.1016/j.jid.2016.08.035

M3 - Article

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EP - 304

JO - Journal of Investigative Dermatology

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