α-Melanocyte-stimulating hormone: A protective peptide against chemotherapy-induced hair follicle damage?

M. Böhm, E. Bodõ, W. Funk, Ralf Paus

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)956-960
Number of pages5
JournalBritish Journal of Dermatology
Volume170
Issue number4
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Melanocyte-Stimulating Hormones
Hair Follicle
Cyclophosphamide
Drug Therapy
Peptides
Heme Oxygenase (Decyclizing)
Alopecia
Protective Agents
Melanins
Pigmentation
Apoptosis
Scalp
Hair
Enzymes
Ultraviolet Rays
Reverse Transcriptase Polymerase Chain Reaction
Keratinocytes
DNA Damage

ASJC Scopus subject areas

  • Dermatology

Cite this

α-Melanocyte-stimulating hormone : A protective peptide against chemotherapy-induced hair follicle damage? / Böhm, M.; Bodõ, E.; Funk, W.; Paus, Ralf.

In: British Journal of Dermatology, Vol. 170, No. 4, 01.01.2014, p. 956-960.

Research output: Contribution to journalArticle

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title = "α-Melanocyte-stimulating hormone: A protective peptide against chemotherapy-induced hair follicle damage?",
abstract = "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.",
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T2 - A protective peptide against chemotherapy-induced hair follicle damage?

AU - Böhm, M.

AU - Bodõ, E.

AU - Funk, W.

AU - Paus, Ralf

PY - 2014/1/1

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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.

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