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001-es BibID:	BIBFORM085361
035-os BibID:	(WoS)000537309400001 (Scopus)85085880838
Első szerző:	Oláh Attila (élettanász)
Cím:	Mitochondrial energy metabolism is negatively regulated by cannabinoid receptor 1 in intact human epidermis / Oláh Attila, Alam Majid, Chéret Jérémy, Kis Nikoletta Gréta, Hegyi Zoltán, Szöllősi Attila Gábor, Vidali Silvia, Bíró Tamás, Paus Ralf
Dátum:	2020
ISSN:	0906-6705
Megjegyzések:	Epidermal energy metabolism is relevant to skin physiology, aging, and photodamage. While selected hormones stimulate epidermal keratinocyte mitochondrial activity, its negative regulation remains unknown. In several cell types, cannabinoid receptor 1 (CB1) is expressed both in the cell membrane (cmCB1), and in the mitochondrial outer membrane (mtCB1), where its stimulation directly suppresses mitochondrial functions. In the current pilot study, we investigated if CB1 is a negative regulator of human epidermal energy metabolism under physiological conditions. Using organ-cultured full-thickness human skin specimens of healthy individuals, we showed that antagonizing the homeostatic CB1 signaling by the administration of the CB1 inverse agonist AM251 increased activity of respiratory chain complex I and II/IV activity in a CB1-dependent manner, since the CB1-selective agonist arachidonyl-2'-chloroethylamide could prevent the effect. Moreover, the phenomenon was also reproduced by siRNA-mediated down-regulation of CB1. As revealed by the unaltered expression of several relevant markers (TFAM, VDAC1, MTCO1, and NDUFS4), modulation of CB1 signaling had no effect on the epidermal mitochondrial mass. Next, by using immunoelectron microscopy, we found that human epidermal keratinocytes express both cmCB1 and mtCB1. Finally, by using equipotent extracellularly-restricted (hemopressin) as well as cell-permeable (AM251) inverse agonists, we found that mitochondrial activity is most likely exclusively regulated by mtCB1. Thus, our data identify mtCB1 as a negative regulator of keratinocyte mitochondrial activity in intact human epidermis, and highlight the question, whether topical therapeutic interventions capable of selectively activating mtCB1 can reduce excessive mitochondrial ROS production resulting from dysregulated mitochondrial activity during skin aging or photodamage.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk endocannabinoid epidermal keratinocyte mitochondrial activity mitochondrially expressed CB1 (mtCB1) cannabinoid receptor 1 (CB1)
Megjelenés:	Experimental Dermatology. - 29 : 7 (2020), p. 616-622. -
További szerzők:	Alam, Majid Chéret, Jérémy Kis Gréta (1979-) (környezetkutató) Hegyi Zoltán (1983-) (molekuláris biológus) Szöllősi Attila Gábor (1982-) (élettanász) Vidali, Silvia Bíró Tamás (1968-) (élettanász) Paus, Ralf
Pályázati támogatás:	121360 OTKA 125055 OTKA Hungarian National Brain Research Program [KTIA_NAP_13-1-2013-001] Egyéb Bolyai János Kutatási Ösztöndíj MTA ITM - Új Nemzeti Kiválóság Program ÚNKP-19-4-DE-287 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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