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Increased melanocyte apoptosis under stress‐mediator Substance P – elucidating pathways involved in stress‐induced premature graying
Author(s) -
Spatz K. R.,
Overall R.,
Klapp B. F.,
Arck P. C.,
Peters E. M. J.
Publication year - 2008
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2008.00742_18.x
Subject(s) - melanocyte , hair follicle , endocrinology , apoptosis , oxidative stress , medicine , biology , programmed cell death , melanin , hair cycle , microbiology and biotechnology , cancer research , melanoma , genetics
Recently, the accumulation of oxidative stress was found to induce apoptosis of hair follicle melanocytes in the pigmentary‐unit during senile hair graying. A disturbance of the well‐balanced melanocyte stress‐regulatory mechanisms by additional oxidative stress caused e.g. by cutaneous inflammation or emotional stress may lead to untimely death of melanocytes. In a noise stress experiment C57BL/6 mice were exposed to a sound stressor for 24 h or received a bolus injection of the neuropeptide stress‐mediator Substance P (SP) during early anagen of the depilation‐induced hair cycle. Back skin was harvested 72 h later. Melanocyte markers such as tyrosinase related peptide (TRP) 1 and TRP 2 were combined with c‐kit to assess activation and with TUNEL‐labelling to assess apoptosis of melanocytes. Exposure to stress or SP resulted in an increase of c‐kit positive melanocytes in the stem cell harbouring bulge region while SP treatment also led to melanocyte–apoptosis in the developing pigmentary‐unit of early anagen hair follicles. These findings suggest a differentiated susceptibility of distinct melanocyte populations in the hair follicle to stressors. On the one hand pigment‐producing melanocytes of the pigmentary‐unit show increased vulnerability towards stress‐mediators, with subsequent premature death during early anagen. On the other hand stress‐mediators have a stimulatory effect on the melanocytes in the stem cell containing hair follicle bulge region. Together this suggests an increased cell turn‐over under stress. Preliminary data from murine telogen full skin microarray analysis also head for a similar two‐sided results. Stressed skin shows up‐regulated genes for cell differentiation, proliferation and immune responses while it shows down‐regulated genes for intracellular signalling cascades and pigmentation. Our results suggest a precocious exhaustion of the melanocyte stem cell pool due to an enhanced turnover of pigment cell precursors as a pathway involved in premature canities.