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001-es BibID:BIBFORM072426
035-os BibID:(WOS)000392469700009 (Scopus)85010461576
Első szerző:Haslam, Iain S.
Cím:Oxidative Damage Control in a Human (Mini-) Organ : Nrf2 Activation Protects against Oxidative Stress-Induced Hair Growth Inhibition / Iain S. Haslam, Laura Jadkauskaite, Imre Lorinc Szabo, Selma Staege, Jasper Hesebeck-Brinckmann, Gail Jenkins, Ranjit K. Bhogal, Fei-Ling Lim, Nilofer Farjo, Bessam Farjo, Tamás Bíró, Matthias Schäfer, Ralf Paus
Dátum:2017
ISSN:0022-202X 1523-1747
Megjegyzések: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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
DERMAL PAPILLA CELLS
IN-VITRO
MITOCHONDRIAL-FUNCTION
FOLLICLE PIGMENTATIONE
PARKINSONS-DISEASE
CYCLOSPORINE-A
CANCER CELLS
CHEMOTHERAPY
CATAGEN
SULFORAPHANE
Megjelenés:Journal Of Investigative Dermatology. - 137 : 2 (2017), p. 295-304. -
További szerzők:Jadkauskaite, Laura Szabó Imre Lőrinc (1987-) (általános orvos) Staege, Selma Hesebeck-Brinckmann, Jasper Jenkins, Gail Bhogal, Ranjit K. Lim, Fei-Ling Farjo, Nilofer Farjo, Bessam Bíró Tamás (1968-) (élettanász) Schäfer, Matthias Paus, Ralf
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