+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

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

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

Journal of Investigative Dermatology 137(2): 295-304

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.

(PDF emailed within 0-6 h: $19.90)

Accession: 058488413

Download citation: RISBibTeXText

PMID: 27702566

DOI: 10.1016/j.jid.2016.08.035

Related references

7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways. International Journal of Molecular Medicine 33(4): 964-970, 2014

Fibroblast growth factor 19 protects the heart from oxidative stress-induced diabetic cardiomyopathy via activation of AMPK/Nrf2/HO-1 pathway. Biochemical and Biophysical Research Communications 502(1): 62-68, 2018

l-carnitine protects human hepatocytes from oxidative stress-induced toxicity through Akt-mediated activation of Nrf2 signaling pathway. Canadian Journal of Physiology and Pharmacology 94(5): 517-525, 2017

Berberine protects immortalized line of human melanocytes from H 2 O 2 -induced oxidative stress via activation of Nrf2 and Mitf signaling pathway. Journal of Dermatological Science 2019, 2019

Caffeoylserotonin protects human keratinocyte HaCaT cells against H2 O2 -induced oxidative stress and apoptosis through upregulation of HO-1 expression via activation of the PI3K/Akt/Nrf2 pathway. PhytoTherapy Research 27(12): 1810-1818, 2014

Caffeoylserotonin Protects Human Keratinocyte HaCaT Cells against H2O2-Induced Oxidative Stress and Apoptosis through Upregulation of HO-1 Expression via Activation of the PI3K/Akt/Nrf2 Pathway. 2013

Activation of Nrf2 by MIND4-17 protects osteoblasts from hydrogen peroxide-induced oxidative stress. Oncotarget 8(62): 105662-105672, 2017

Genetic activation of Nrf2 protects against fasting-induced oxidative stress in livers of mice. Plos One 8(3): E59122, 2013

Protective Effect of Phloroglucinol on Oxidative Stress-Induced DNA Damage and Apoptosis through Activation of the Nrf2/HO-1 Signaling Pathway in HaCaT Human Keratinocytes. Marine Drugs 17(4), 2019

Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage. Skin Pharmacology and Physiology 2019: 1-9, 2019

Resveratrol protects primary rat hepatocytes against oxidative stress damage: activation of the Nrf2 transcription factor and augmented activities of antioxidant enzymes. European Journal of Pharmacology 591(1-3): 66-72, 2008

Celastrol Protects RPE Cells from Oxidative Stress-Induced Cell Death via Activation of Nrf2 Signaling Pathway. Current Molecular Medicine 2019, 2019

The Ethanol Extract of Licorice (Glycyrrhiza uralensis) Protects against Triptolide-Induced Oxidative Stress through Activation of Nrf2. Evidence-Based Complementary and Alternative Medicine 2017: 2752389, 2017

Homoeriodictyol protects human endothelial cells against oxidative insults through activation of Nrf2 and inhibition of mitochondrial dysfunction. Vascular Pharmacology 109: 72-82, 2018

Glycyrrhizin protects human melanocytes from H2O2‑induced oxidative damage via the Nrf2‑dependent induction of HO‑1. International Journal of Molecular Medicine 2019, 2019