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Stress-sensing in the human greying hair follicle: Ataxia Telangiectasia Mutated (ATM) depletion in hair bulb melanocytes in canities-prone scalp.
Sci Rep. 2020 10 30; 10(1):18711.SR

Abstract

Canities (or hair greying) is an age-linked loss of the natural pigment called melanin from hair. While the specific cause(s) underlying the loss of melanogenically-active melanocytes from the anagen hair bulbs of affected human scalp remains unclear, oxidative stress sensing appears to be a key factor involved. In this study, we examined the follicular melanin unit in variably pigmented follicles from the aging human scalp of healthy individuals (22-70 years). Over 20 markers were selected within the following categories: melanocyte-specific, apoptosis, cell cycle, DNA repair/damage, senescence and oxidative stress. As expected, a reduction in melanocyte-specific markers in proportion to the extent of canities was observed. A major finding of our study was the intense and highly specific nuclear expression of Ataxia Telangiectasia Mutated (ATM) protein within melanocytes in anagen hair follicle bulbs. ATM is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks and functions as an important sensor of reactive oxygen species (ROS) in human cells. The incidence and expression level of ATM correlated with pigmentary status in canities-affected hair follicles. Moreover, increased staining of the redox-associated markers 8-OHdG, GADD45 and GP-1 were also detected within isolated bulbar melanocytes, although this change was not clearly associated with donor age or canities extent. Surprisingly, we were unable to detect any specific change in the expression of other markers of oxidative stress, senescence or DNA damage/repair in the canities-affected melanocytes compared to surrounding bulbar keratinocytes. By contrast, several markers showed distinct expression of markers for oxidative stress and apoptosis/differentiation in the inner root sheath (IRS) as well as other parts of the hair follicle. Using our in vitro model of primary human scalp hair follicle melanocytes, we showed that ATM expression increased after incubation with the pro-oxidant hydrogen peroxide (H2O2). In addition, this ATM increase was prevented by pre-incubation of cells with antioxidants. The relationship between ATM and redox stress sensing was further evidenced as we observed that the inhibition of ATM expression by chemical inhibition promoted the loss of melanocyte viability induced by oxidative stress. Taken together these new findings illustrate the key role of ATM in the protection of human hair follicle melanocytes from oxidative stress/damage within the human scalp hair bulb. In conclusion, these results highlight the remarkable complexity and role of redox sensing in the status of human hair follicle growth, differentiation and pigmentation.

Authors+Show Affiliations

Centre for Skin Sciences, School of Life Sciences, University of Bradford, Richmond Rd., Bradford, BD7 1DP, West Yorkshire, UK. s.k.sikkink@bradford.ac.uk.BASF Beauty Care Solutions France S.A.S., Pulnoy, France.BASF Beauty Care Solutions France S.A.S., Pulnoy, France.BASF Beauty Care Solutions France S.A.S., Pulnoy, France.Centre for Skin Sciences, School of Life Sciences, University of Bradford, Richmond Rd., Bradford, BD7 1DP, West Yorkshire, UK. desmond.tobin@ucd.ie. The Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin 4, Ireland. desmond.tobin@ucd.ie.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33128003

Citation

Sikkink, Stephen K., et al. "Stress-sensing in the Human Greying Hair Follicle: Ataxia Telangiectasia Mutated (ATM) Depletion in Hair Bulb Melanocytes in Canities-prone Scalp." Scientific Reports, vol. 10, no. 1, 2020, p. 18711.
Sikkink SK, Mine S, Freis O, et al. Stress-sensing in the human greying hair follicle: Ataxia Telangiectasia Mutated (ATM) depletion in hair bulb melanocytes in canities-prone scalp. Sci Rep. 2020;10(1):18711.
Sikkink, S. K., Mine, S., Freis, O., Danoux, L., & Tobin, D. J. (2020). Stress-sensing in the human greying hair follicle: Ataxia Telangiectasia Mutated (ATM) depletion in hair bulb melanocytes in canities-prone scalp. Scientific Reports, 10(1), 18711. https://doi.org/10.1038/s41598-020-75334-9
Sikkink SK, et al. Stress-sensing in the Human Greying Hair Follicle: Ataxia Telangiectasia Mutated (ATM) Depletion in Hair Bulb Melanocytes in Canities-prone Scalp. Sci Rep. 2020 10 30;10(1):18711. PubMed PMID: 33128003.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stress-sensing in the human greying hair follicle: Ataxia Telangiectasia Mutated (ATM) depletion in hair bulb melanocytes in canities-prone scalp. AU - Sikkink,Stephen K, AU - Mine,Solene, AU - Freis,Olga, AU - Danoux,Louis, AU - Tobin,Desmond J, Y1 - 2020/10/30/ PY - 2020/02/10/received PY - 2020/10/12/accepted PY - 2020/10/31/entrez PY - 2020/11/1/pubmed PY - 2021/3/4/medline SP - 18711 EP - 18711 JF - Scientific reports JO - Sci Rep VL - 10 IS - 1 N2 - Canities (or hair greying) is an age-linked loss of the natural pigment called melanin from hair. While the specific cause(s) underlying the loss of melanogenically-active melanocytes from the anagen hair bulbs of affected human scalp remains unclear, oxidative stress sensing appears to be a key factor involved. In this study, we examined the follicular melanin unit in variably pigmented follicles from the aging human scalp of healthy individuals (22-70 years). Over 20 markers were selected within the following categories: melanocyte-specific, apoptosis, cell cycle, DNA repair/damage, senescence and oxidative stress. As expected, a reduction in melanocyte-specific markers in proportion to the extent of canities was observed. A major finding of our study was the intense and highly specific nuclear expression of Ataxia Telangiectasia Mutated (ATM) protein within melanocytes in anagen hair follicle bulbs. ATM is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks and functions as an important sensor of reactive oxygen species (ROS) in human cells. The incidence and expression level of ATM correlated with pigmentary status in canities-affected hair follicles. Moreover, increased staining of the redox-associated markers 8-OHdG, GADD45 and GP-1 were also detected within isolated bulbar melanocytes, although this change was not clearly associated with donor age or canities extent. Surprisingly, we were unable to detect any specific change in the expression of other markers of oxidative stress, senescence or DNA damage/repair in the canities-affected melanocytes compared to surrounding bulbar keratinocytes. By contrast, several markers showed distinct expression of markers for oxidative stress and apoptosis/differentiation in the inner root sheath (IRS) as well as other parts of the hair follicle. Using our in vitro model of primary human scalp hair follicle melanocytes, we showed that ATM expression increased after incubation with the pro-oxidant hydrogen peroxide (H2O2). In addition, this ATM increase was prevented by pre-incubation of cells with antioxidants. The relationship between ATM and redox stress sensing was further evidenced as we observed that the inhibition of ATM expression by chemical inhibition promoted the loss of melanocyte viability induced by oxidative stress. Taken together these new findings illustrate the key role of ATM in the protection of human hair follicle melanocytes from oxidative stress/damage within the human scalp hair bulb. In conclusion, these results highlight the remarkable complexity and role of redox sensing in the status of human hair follicle growth, differentiation and pigmentation. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/33128003/Stress_sensing_in_the_human_greying_hair_follicle:_Ataxia_Telangiectasia_Mutated__ATM__depletion_in_hair_bulb_melanocytes_in_canities_prone_scalp_ DB - PRIME DP - Unbound Medicine ER -