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Efficacy of the melanocortin analogue Nle4-D-Phe7-α-melanocyte-stimulating hormone in the treatment of patients with Hailey-Hailey disease.

Biolcati G, Aurizi C, Barbieri L, Cialfi S, Screpanti I, Talora C - Clin. Exp. Dermatol. (2013)

Bottom Line: Our results show that Nrf2 is an important target of the afamelanotide signalling that reduces oxidative stress.Because afamelanotide possesses antioxidant effects, we also assessed the clinical potential of this α-MSH analogue in the treatment of patients with HHD.Afamelanotide is effective for the treatment of skin lesions in HHD.

View Article: PubMed Central - PubMed

Affiliation: Porphyria Center, San Gallicano Institute IRCCS, Rome, Italy.

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Related in: MedlinePlus

(a–d) Experiments carried out in primary keratinocytes derived from normal-appearing (N) or lesioned (L) skin of one or more of three patients (P1, P2 and P3) with Hailey–Hailey disease (HHD). (a) Total RNA (arbitrary units). *P < 0.001 compared with control. (b) The top bands show the reduction in protein expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in lesioned skin compared with normal-appearing skin. The same blot was then stripped and reprobed with anti-tubulin antibodies. Lane 3 shows the keratinocytes that had been treated with the α-melanocyte-stimulating hormone analogue afamelanotide; the reduction in Nrf2 was lessened. (c) DNA synthesis in keratinocytes derived from healthy donors (normal human keratinocytes; NHK), and from normal-appearing and lesioned skin from patients with HHD, with or without afamelanotide treatment. Cells were pulse-labelled with 3H-thymidine for 12 h. All samples were tested in triplicate. Error bars indicate standard deviation. (d) Protein expression of the melanocortin receptor MC5R in total cell extracts (60 microgram) prepared from normal keratinocytes (NKC) derived from the normal-appearing skin biopsies of P1 and P2. The same blot was then stripped and reprobed with anti-tubulin antibodies. Lane 1 shows the control whole cell extract 10 microgram (HEK293 cells transfected with MC5R cDNA).
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fig01: (a–d) Experiments carried out in primary keratinocytes derived from normal-appearing (N) or lesioned (L) skin of one or more of three patients (P1, P2 and P3) with Hailey–Hailey disease (HHD). (a) Total RNA (arbitrary units). *P < 0.001 compared with control. (b) The top bands show the reduction in protein expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in lesioned skin compared with normal-appearing skin. The same blot was then stripped and reprobed with anti-tubulin antibodies. Lane 3 shows the keratinocytes that had been treated with the α-melanocyte-stimulating hormone analogue afamelanotide; the reduction in Nrf2 was lessened. (c) DNA synthesis in keratinocytes derived from healthy donors (normal human keratinocytes; NHK), and from normal-appearing and lesioned skin from patients with HHD, with or without afamelanotide treatment. Cells were pulse-labelled with 3H-thymidine for 12 h. All samples were tested in triplicate. Error bars indicate standard deviation. (d) Protein expression of the melanocortin receptor MC5R in total cell extracts (60 microgram) prepared from normal keratinocytes (NKC) derived from the normal-appearing skin biopsies of P1 and P2. The same blot was then stripped and reprobed with anti-tubulin antibodies. Lane 1 shows the control whole cell extract 10 microgram (HEK293 cells transfected with MC5R cDNA).

Mentions: Real-time RT-PCR analysis showed that Nrf2 mRNA was significantly downregulated in keratinocytes derived from cutaneous lesions of patients with HHD (Fig.1a). These results were confirmed by the western blotting of keratinocyte lysates from patients 1 and 2 (Fig.1b).


Efficacy of the melanocortin analogue Nle4-D-Phe7-α-melanocyte-stimulating hormone in the treatment of patients with Hailey-Hailey disease.

Biolcati G, Aurizi C, Barbieri L, Cialfi S, Screpanti I, Talora C - Clin. Exp. Dermatol. (2013)

(a–d) Experiments carried out in primary keratinocytes derived from normal-appearing (N) or lesioned (L) skin of one or more of three patients (P1, P2 and P3) with Hailey–Hailey disease (HHD). (a) Total RNA (arbitrary units). *P < 0.001 compared with control. (b) The top bands show the reduction in protein expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in lesioned skin compared with normal-appearing skin. The same blot was then stripped and reprobed with anti-tubulin antibodies. Lane 3 shows the keratinocytes that had been treated with the α-melanocyte-stimulating hormone analogue afamelanotide; the reduction in Nrf2 was lessened. (c) DNA synthesis in keratinocytes derived from healthy donors (normal human keratinocytes; NHK), and from normal-appearing and lesioned skin from patients with HHD, with or without afamelanotide treatment. Cells were pulse-labelled with 3H-thymidine for 12 h. All samples were tested in triplicate. Error bars indicate standard deviation. (d) Protein expression of the melanocortin receptor MC5R in total cell extracts (60 microgram) prepared from normal keratinocytes (NKC) derived from the normal-appearing skin biopsies of P1 and P2. The same blot was then stripped and reprobed with anti-tubulin antibodies. Lane 1 shows the control whole cell extract 10 microgram (HEK293 cells transfected with MC5R cDNA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4255790&req=5

fig01: (a–d) Experiments carried out in primary keratinocytes derived from normal-appearing (N) or lesioned (L) skin of one or more of three patients (P1, P2 and P3) with Hailey–Hailey disease (HHD). (a) Total RNA (arbitrary units). *P < 0.001 compared with control. (b) The top bands show the reduction in protein expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in lesioned skin compared with normal-appearing skin. The same blot was then stripped and reprobed with anti-tubulin antibodies. Lane 3 shows the keratinocytes that had been treated with the α-melanocyte-stimulating hormone analogue afamelanotide; the reduction in Nrf2 was lessened. (c) DNA synthesis in keratinocytes derived from healthy donors (normal human keratinocytes; NHK), and from normal-appearing and lesioned skin from patients with HHD, with or without afamelanotide treatment. Cells were pulse-labelled with 3H-thymidine for 12 h. All samples were tested in triplicate. Error bars indicate standard deviation. (d) Protein expression of the melanocortin receptor MC5R in total cell extracts (60 microgram) prepared from normal keratinocytes (NKC) derived from the normal-appearing skin biopsies of P1 and P2. The same blot was then stripped and reprobed with anti-tubulin antibodies. Lane 1 shows the control whole cell extract 10 microgram (HEK293 cells transfected with MC5R cDNA).
Mentions: Real-time RT-PCR analysis showed that Nrf2 mRNA was significantly downregulated in keratinocytes derived from cutaneous lesions of patients with HHD (Fig.1a). These results were confirmed by the western blotting of keratinocyte lysates from patients 1 and 2 (Fig.1b).

Bottom Line: Our results show that Nrf2 is an important target of the afamelanotide signalling that reduces oxidative stress.Because afamelanotide possesses antioxidant effects, we also assessed the clinical potential of this α-MSH analogue in the treatment of patients with HHD.Afamelanotide is effective for the treatment of skin lesions in HHD.

View Article: PubMed Central - PubMed

Affiliation: Porphyria Center, San Gallicano Institute IRCCS, Rome, Italy.

Show MeSH
Related in: MedlinePlus