Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

Abstract

Since it is unknown whether thyroid hormones (THs) regulate mitochondrial function in human epidermis, we treated organ-cultured human skin, or isolated cultured human epidermal keratinocytes, with triiodothyronine (100 pmol/L) or thyroxine (100 nmol/L). Both THs significantly increased protein expression of the mitochondrially encoded cytochrome C oxidase I (MTCO1), complex I activity, and the number of perinuclear mitochondria. Triiodothyronine also increased mitochondrial transcription factor A (TFAM) protein expression, and thyroxine stimulated complex II/IV activity. Increased mitochondrial function can correlate with increased reactive oxygen species production, DNA damage, and accelerated tissue aging. However, THs neither raised reactive oxygen species production or matrix metalloproteinase-1, -2 and -9 activity nor decreased sirtuin1 (Sirt1) immunoreactivity. Instead, triiodothyronine increased sirtuin-1, fibrillin-1, proliferator-activated receptor-gamma 1-alpha (PGC1α), collagen I and III transcription, and thyroxine decreased cyclin-dependent kinase inhibitor 2A (p16(ink4)) expression in organ-cultured human skin. Moreover, TH treatment increased intracutaneous fibrillin-rich microfibril and collagen III deposition and decreased mammalian target of rapamycin (mTORC1/2) expression ex vivo. This identifies THs as potent endocrine stimulators of mitochondrial function in human epidermis, which down-regulates rather than enhance the expression of skin aging-related biomarkers ex vivo. Therefore, topically applied THs deserve further exploration as candidate agents for treating skin conditions characterized by reduced mitochondrial function.

Theophylline exerts complex anti‐ageing and anti‐cytotoxicity effects in human skin ex vivo

“…The samples were obtained with informed patient consent and approval from the University of Muenster Ethics Committee, adhering to Helsinki guidelines. The samples were prepared as 4‐mm punch samples and used for full‐thickness human skin organ culture serum‐free conditions as described previously . The samples were kept free‐floating in serum‐free medium.…”

“…Ab23446) and anti‐collagen III (1:500; AbCam, Ab2345) . As a secondary antibody, a goat anti‐rabbit FITC (1:200; Jackson ImmunoResearch) was used .…”

“…It serves as a marker for both extrinsic and intrinsic ageing of the skin . Fibrillin‐1 IR was detected in acetone‐fixed cryosections using mouse monoclonal anti‐fibrillin‐1 (1:200; AbCam, Ab3090) . As a secondary antibody, a rhodamine‐conjugated goat anti‐mouse antibody (1:200; Jackson ImmunoResearch) was used.…”

“…In addition, we assessed in situ epidermal keratinocyte apoptosis and proliferation by Ki‐67/TUNEL immunostaining , and epidermal progenitor cell numbers by immunostaining for the stem cell marker keratin 15 (K15) . ECM stability in situ was evaluated by immunostaining for collagen I and III and fibrillin‐1 , mitochondrial activity was examined by staining for MTCO1, and the ageing phenotype by sirtuin‐1 . Moreover, we explored in situ , epidermal pigmentation by Masson Fontana histochemistry , and the expression of a major endogenous anti‐oxidant, metallothionein by immunostaining.…”

Terá a melatonina uma ação fotoprotetora cutânea? Uma revisão baseada na evidência

“…Esse eixo seria uma função do sistema melatoninérgico cutâneo, pelo qual a mitocêndria poderia ser capaz de ajustar a disponibilidade de espécies reativas de oxigénio durante o processo de regeneração da pele e cicatrização de feridas. [54][55] De facto, um outro estudo propõe a melatonina como arma dum sistema bioquímico antigo de proteção da célula em relação a noxas exteriores e interiores, tendo em conta a origem filogenética da melatonina há 2,5 mil milhões de anos e a sua função primordial de defesa da pele, conservada ao longo da evolução. 55 In vitro verificou-se um efeito fotoprotetor em culturas de células e de órgãos contra radiação UVB pela melatonina e por metabolitos e compostos da via da melatonina; verificou-se que conseguiram reverter o dano UVB-induzido em queratinócitos e melanócitos e que a proteção da melatonina se estende aos fibroblastos da derme.…”