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Peroxisome proliferator-activated receptor activators protect sebocytes from apoptosis: a new treatment modality for acne?
Br J Dermatol. 2011 Jan; 164(1):182-6.BJ

Abstract

BACKGROUND

The main function of the human sebaceous gland is sebum excretion. Increased sebum levels combined with follicular hyperkeratinization are a prerequisite of acne vulgaris. As peroxisome proliferator-activated receptors (PPARs) are known to control lipid metabolism in several human tissues they have been considered to be involved in the pathogenesis of acne vulgaris.

OBJECTIVES

To investigate the effect of activators of PPAR-α (WY14643), PPAR-γ (rosiglitazone) and PPAR-δ (L-165.041) on basal and staurosporine-induced apoptosis in the human sebocyte cell line SZ95 in vitro.

METHODS

After defining the basal effects of PPAR activators on membrane integrity (lactate dehydrogenase release) and DNA synthesis (5-bromodeoxyuridine incorporation), apoptosis was determined by the release of histone-associated DNA fragments. The underlying signalling events were detected by Western blotting and the use of specific inhibitors against p44/42 and protein kinase B (PKB)/Akt.

RESULTS

PPAR activators of all three subsets offer antiapoptotic effects, with L-165.041 being the most potent. This compound induced the activation of PKB/Akt and p44/42, two kinases involved in antiapoptosis and proliferation, respectively. An inhibition of these kinases by specific inhibitors reversed the suppression of histone-associated DNA fragments by L-165.041, indicating that these signalling pathways participate in the observed antiapoptotic effect.

CONCLUSIONS

The present data suggest that activators of PPAR, in particular of the δ subset, might have beneficial effects on acne vulgaris by inhibiting the release of lipids in the context of sebocyte apoptosis.

Authors+Show Affiliations

Department of Dermatology, Venereology and Allergology, University Hospital, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, Frankfurt/Main 60590, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21091942

Citation

Schuster, M, et al. "Peroxisome Proliferator-activated Receptor Activators Protect Sebocytes From Apoptosis: a New Treatment Modality for Acne?" The British Journal of Dermatology, vol. 164, no. 1, 2011, pp. 182-6.
Schuster M, Zouboulis CC, Ochsendorf F, et al. Peroxisome proliferator-activated receptor activators protect sebocytes from apoptosis: a new treatment modality for acne? Br J Dermatol. 2011;164(1):182-6.
Schuster, M., Zouboulis, C. C., Ochsendorf, F., Müller, J., Thaçi, D., Bernd, A., Kaufmann, R., & Kippenberger, S. (2011). Peroxisome proliferator-activated receptor activators protect sebocytes from apoptosis: a new treatment modality for acne? The British Journal of Dermatology, 164(1), 182-6. https://doi.org/10.1111/j.1365-2133.2010.10037.x
Schuster M, et al. Peroxisome Proliferator-activated Receptor Activators Protect Sebocytes From Apoptosis: a New Treatment Modality for Acne. Br J Dermatol. 2011;164(1):182-6. PubMed PMID: 21091942.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peroxisome proliferator-activated receptor activators protect sebocytes from apoptosis: a new treatment modality for acne? AU - Schuster,M, AU - Zouboulis,C C, AU - Ochsendorf,F, AU - Müller,J, AU - Thaçi,D, AU - Bernd,A, AU - Kaufmann,R, AU - Kippenberger,S, Y1 - 2010/11/23/ PY - 2010/11/25/entrez PY - 2010/11/26/pubmed PY - 2011/4/28/medline SP - 182 EP - 6 JF - The British journal of dermatology JO - Br. J. Dermatol. VL - 164 IS - 1 N2 - BACKGROUND: The main function of the human sebaceous gland is sebum excretion. Increased sebum levels combined with follicular hyperkeratinization are a prerequisite of acne vulgaris. As peroxisome proliferator-activated receptors (PPARs) are known to control lipid metabolism in several human tissues they have been considered to be involved in the pathogenesis of acne vulgaris. OBJECTIVES: To investigate the effect of activators of PPAR-α (WY14643), PPAR-γ (rosiglitazone) and PPAR-δ (L-165.041) on basal and staurosporine-induced apoptosis in the human sebocyte cell line SZ95 in vitro. METHODS: After defining the basal effects of PPAR activators on membrane integrity (lactate dehydrogenase release) and DNA synthesis (5-bromodeoxyuridine incorporation), apoptosis was determined by the release of histone-associated DNA fragments. The underlying signalling events were detected by Western blotting and the use of specific inhibitors against p44/42 and protein kinase B (PKB)/Akt. RESULTS: PPAR activators of all three subsets offer antiapoptotic effects, with L-165.041 being the most potent. This compound induced the activation of PKB/Akt and p44/42, two kinases involved in antiapoptosis and proliferation, respectively. An inhibition of these kinases by specific inhibitors reversed the suppression of histone-associated DNA fragments by L-165.041, indicating that these signalling pathways participate in the observed antiapoptotic effect. CONCLUSIONS: The present data suggest that activators of PPAR, in particular of the δ subset, might have beneficial effects on acne vulgaris by inhibiting the release of lipids in the context of sebocyte apoptosis. SN - 1365-2133 UR - https://www.unboundmedicine.com/medline/citation/21091942/Peroxisome_proliferator_activated_receptor_activators_protect_sebocytes_from_apoptosis:_a_new_treatment_modality_for_acne L2 - https://doi.org/10.1111/j.1365-2133.2010.10037.x DB - PRIME DP - Unbound Medicine ER -