Hair exerts a range of functions including thermoregulation, physical protection, sensory activity. Mature and actively growing hair follicles become anchored in the subcutis, and regenerate by spontaneous repetitive cycles of growth (anagen), apoptosis-driven regression (catagen), and quiescence (telogen). We focused our study on investigating the effect of new therapeutic molecules capable of counteracting the regression phase. We have tested our working hypothesis on HFDPC cells, grown in culture in Follicle Dermal Papilla Growth Medium, and apoptosis was induced by 24 hours incubation with 1 μM staurosporin. This treatment resulted in a marked activation of Caspase-3 accompanied by cytoskeletal degradation, nuclear blebbing, and cellular fragmentation. The addition of spermidin or rutine in the micromolar range concentration reduced staurosporin-induced caspase activity by over 50%, when the two agents were added simultaneously equal levels of caspase-3 inhibition was achieved with concentration 10 fold lower. Zeaxantine alone was ineffective, however when added to the combined spermidin and rutine treatment, the staurosporin-induced caspase activity was almost totally counteracted and the enzymatic activity was significantly reduced. These combined treatment was also effective in preventing staurosporin-mediated cellular damage. The extent of cell loss was greatly reduced and there was a total preservation and normal distribution of actin-tubulin cytoskeleton with normal cellular shape. Interestingly, our combined treatment also counteracted caspase-3 over-expression induced by staurosporin. In conclusion, this sperimental molecules can counteract HFDPC cells apoptosis and may represent an effective preventing treatment for the catagen phase of the hair bulb life cycle.

NEW NON SYNTHETIC MOLECULES ARE ABLE TO INHIBIT APOPTOSIS IN DERMAL PAPILLAR CELLS OF HAIR BULB

TRAVERSA, MARIA VITTORIA
2011

Abstract

Hair exerts a range of functions including thermoregulation, physical protection, sensory activity. Mature and actively growing hair follicles become anchored in the subcutis, and regenerate by spontaneous repetitive cycles of growth (anagen), apoptosis-driven regression (catagen), and quiescence (telogen). We focused our study on investigating the effect of new therapeutic molecules capable of counteracting the regression phase. We have tested our working hypothesis on HFDPC cells, grown in culture in Follicle Dermal Papilla Growth Medium, and apoptosis was induced by 24 hours incubation with 1 μM staurosporin. This treatment resulted in a marked activation of Caspase-3 accompanied by cytoskeletal degradation, nuclear blebbing, and cellular fragmentation. The addition of spermidin or rutine in the micromolar range concentration reduced staurosporin-induced caspase activity by over 50%, when the two agents were added simultaneously equal levels of caspase-3 inhibition was achieved with concentration 10 fold lower. Zeaxantine alone was ineffective, however when added to the combined spermidin and rutine treatment, the staurosporin-induced caspase activity was almost totally counteracted and the enzymatic activity was significantly reduced. These combined treatment was also effective in preventing staurosporin-mediated cellular damage. The extent of cell loss was greatly reduced and there was a total preservation and normal distribution of actin-tubulin cytoskeleton with normal cellular shape. Interestingly, our combined treatment also counteracted caspase-3 over-expression induced by staurosporin. In conclusion, this sperimental molecules can counteract HFDPC cells apoptosis and may represent an effective preventing treatment for the catagen phase of the hair bulb life cycle.
28-gen-2011
Inglese
HFDP cells ; androgenetic alopecia ; apoptosis ; caspase-3 ; non synthetic molecules
GORIO, ALFREDO
Università degli Studi di Milano
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/103352
Il codice NBN di questa tesi è URN:NBN:IT:UNIMI-103352