Maintenance of Grp94 expression is sufficient to counter unloading atrophy and oxidative stress by mechanistically stabilizing nNOS-multiprotein complex at the myofiber sarcolemma.

ObjectivesAlthough the effect of ultraviolet radiation (UVR) on human skin has been extensively studied, very little is known on how UVR impacts on hair follicle (HF) homeostasis. Here, we investigated how solar spectrum UVR that hits the human skin surface impacts on HF biology, and whether any detrimental effects can be mitigated by a widely used cosmetic and nutraceutical ingredient, caffeine.MethodsHuman scalp skin with terminal HFs was irradiated transepidermally ex vivo using either 10 J/cm2 UVA (340–440 nm) + 20 mJ/cm2 UVB (290–320 nm) (low dose) or 50 J/cm2 UVA + 50 mJ/cm2 UVB (high dose) and organ‐cultured under serum‐free conditions for 1 or 3 days. 0.1% caffeine (5.15 mmol/L) was topically applied for 3 days prior to UV exposure with 40 J/cm2 UVA + 40 mJ/cm2 UVB and for 3 days after UVR. The effects on various toxicity and vitality read‐out parameters were measured in defined skin and HF compartments.ResultsConsistent with previous results, transepidermal UVR exerted skin cytotoxicity and epidermal damage. Treatment with high and/or low UVA+UVB doses also induced oxidative DNA damage and cytotoxicity in human HFs. In addition, it decreased proliferation and promoted apoptosis of HF outer root sheath (ORS) and hair matrix (HM) keratinocytes, stimulated catagen development, differentially regulated the expression of HF growth factors, and induced perifollicular mast cell degranulation. UVR‐mediated HF damage was more severe after irradiation with high UVR dose and reached also proximal HF compartments. The topical application of 0.1% caffeine did not induce skin or HF cytotoxicity and stimulated the expression of IGF‐1 in the proximal HF ORS. However, it promoted keratinocyte apoptosis in selected HF compartments. Moreover, caffeine provided protection towards UVR‐mediated HF cytotoxicity and dystrophy, keratinocyte apoptosis, and tendential up‐regulation of the catagen‐promoting growth factor.ConclusionOur study highlights the clinical relevance of our scalp UV irradiation ex vivo assay and provides the first evidence that transepidermal UV radiation negatively affects important human HF functions. This suggests that it is a sensible prophylactic strategy to integrate agents such as caffeine that can act as HF photoprotectants into sun‐protective cosmeceutical and nutraceutical formulations.

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