TY - JOUR
T1 - α-Melanocyte-stimulating hormone
T2 - A protective peptide against chemotherapy-induced hair follicle damage?
AU - Böhm, M.
AU - Bodõ, E.
AU - Funk, W.
AU - Paus, R.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Background Effective, safe and well-tolerated therapeutic and/or preventive regimens for chemotherapy-induced alopecia (CIA) still remain to be developed. Because α-melanocyte-stimulating hormone (α-MSH) exerts a number of cytoprotective effects and is well tolerated, we hypothesized that it may be a candidate CIA-protective agent. Objectives To explore, using a human in vitro model for chemotherapy-induced hair follicle (HF) dystrophy that employs the key cyclophosphamide metabolite (4-hydroperoxy-cyclophosphamide, 4-HC), whether α-MSH protects from 4-HC-induced HF dystrophy. Methods Microdissected human scalp HFs from four individuals were treated with 4-HC, α-MSH and 4-HC plus α-MSH. Changes in HF cycling, melanin distribution and hair matrix keratinocyte proliferation/apoptosis were examined by quantitative (immune-) morphometry. Expression of the cytoprotective enzyme haem oxygenase-1 (HO-1) was determined by real-time reverse transcriptase-polymerase chain reaction in HF of two individuals. Results In 50% of the individuals α-MSH reduced melanin clumping as an early sign of 4-HC-induced disruption of follicular pigmentation. α-MSH reduced 4-HC-induced apoptosis in the HFs of one female patient. These protective effects of α-MSH were not associated with changes in 4-HC-induced catagen induction. α-MSH and 4-HC both increased HO-1 mRNA expression, while the combination of both agents had additive effects on HO-1 transcription. Conclusions Exogenous α-MSH exerts moderate HF-protective effects against 4-HC-induced human scalp HF damage and upregulates the intrafollicular expression of a key cytoprotective enzyme. However, as substantial interindividual response variations were found, further studies are needed to probe α-MSH as a candidate CIA-protective agent. What's already known about this topic? Better therapeutic or preventive regimens for chemotherapy-induced alopecia are urgently needed. Because α-melanocyte-stimulating hormone (α-MSH) can counteract genotoxic and oxidative stress induced by ultraviolet light we investigated if this peptide is cytoprotective in an in vitro model of chemotherapy-induced hair dystrophy. What does this study add? α-MSH reduced 4-hydroperoxy- cyclophosphamide-induced apoptosis and disruption of pigmentation in organ-cultured hair follicles of some patients. These effects of α-MSH were associated with increased haem oxygenase-1 expression.
AB - Background Effective, safe and well-tolerated therapeutic and/or preventive regimens for chemotherapy-induced alopecia (CIA) still remain to be developed. Because α-melanocyte-stimulating hormone (α-MSH) exerts a number of cytoprotective effects and is well tolerated, we hypothesized that it may be a candidate CIA-protective agent. Objectives To explore, using a human in vitro model for chemotherapy-induced hair follicle (HF) dystrophy that employs the key cyclophosphamide metabolite (4-hydroperoxy-cyclophosphamide, 4-HC), whether α-MSH protects from 4-HC-induced HF dystrophy. Methods Microdissected human scalp HFs from four individuals were treated with 4-HC, α-MSH and 4-HC plus α-MSH. Changes in HF cycling, melanin distribution and hair matrix keratinocyte proliferation/apoptosis were examined by quantitative (immune-) morphometry. Expression of the cytoprotective enzyme haem oxygenase-1 (HO-1) was determined by real-time reverse transcriptase-polymerase chain reaction in HF of two individuals. Results In 50% of the individuals α-MSH reduced melanin clumping as an early sign of 4-HC-induced disruption of follicular pigmentation. α-MSH reduced 4-HC-induced apoptosis in the HFs of one female patient. These protective effects of α-MSH were not associated with changes in 4-HC-induced catagen induction. α-MSH and 4-HC both increased HO-1 mRNA expression, while the combination of both agents had additive effects on HO-1 transcription. Conclusions Exogenous α-MSH exerts moderate HF-protective effects against 4-HC-induced human scalp HF damage and upregulates the intrafollicular expression of a key cytoprotective enzyme. However, as substantial interindividual response variations were found, further studies are needed to probe α-MSH as a candidate CIA-protective agent. What's already known about this topic? Better therapeutic or preventive regimens for chemotherapy-induced alopecia are urgently needed. Because α-melanocyte-stimulating hormone (α-MSH) can counteract genotoxic and oxidative stress induced by ultraviolet light we investigated if this peptide is cytoprotective in an in vitro model of chemotherapy-induced hair dystrophy. What does this study add? α-MSH reduced 4-hydroperoxy- cyclophosphamide-induced apoptosis and disruption of pigmentation in organ-cultured hair follicles of some patients. These effects of α-MSH were associated with increased haem oxygenase-1 expression.
UR - http://www.scopus.com/inward/record.url?scp=84908172859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908172859&partnerID=8YFLogxK
U2 - 10.1111/bjd.12759
DO - 10.1111/bjd.12759
M3 - Article
C2 - 24341930
AN - SCOPUS:84908172859
VL - 170
SP - 956
EP - 960
JO - British Journal of Dermatology
JF - British Journal of Dermatology
SN - 0007-0963
IS - 4
ER -