Department of Dermatology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, P.R. China.
Department of Dermatology, Cangzhou City People's Hospital, Cangzhou, Hebei 061000, P.R. China.
Int J Mol Med. 2018 Jun;41(6):3653-3661. doi: 10.3892/ijmm.2018.3550. Epub 2018 Mar 7.
Chronic ultraviolet (UV) exposure-induced oxidative stress is associated with the pathogenesis of skin damage. However, the nuclear factor erythroid‑2‑related factor 2 (Nrf2) pathway is a critical factor in protecting cells against UVB‑induced injury through inhibiting oxidative stress. Furthermore, Nrf2 activation requires the involvement of the phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) pathway, which has a major role in survival of various cell types. Molecular hydrogen exerts protective effects on UV‑induced injury, but the underlying mechanisms have remained elusive. The present study assessed the protective effects of hydrogen against oxidative stress‑induced injury caused by UVB irradiation and investigated the molecular mechanisms. In vitro, UVB‑induced HaCaT cells were collected for the detection of reactive oxygen species, 8‑iso‑prostaglandin F2α, malondialdehyde via fluorescence spectrometry and ELISA; cell activity and cytotoxicity by MTT and lactate dehydrogenase assays, respectively. Additionally, the expression level of PI3K, Akt, Nrf2 and heme oxygenase‑1 (HO‑1) were investigated using western blot, etc. All of the results indicated that hydrogen decreased the levels of reactive oxygen species, 8‑iso‑prostaglandin F2α and malondialdehyde, and promoted the UVB exposure‑induced expression of PI3K, Akt, Nrf2 and heme oxygenase‑1 in HaCaT cells. Of note, PI3K inhibition partially reversed the effects of hydrogen on UVB‑induced HaCaT cells. Therefore, hydrogen effectively protects cells from UVB radiation‑induced oxidative stress by inhibiting Nrf2/HO‑1 activation through the PI3K/Akt signaling pathway.
慢性紫外线 (UV) 暴露引起的氧化应激与皮肤损伤的发病机制有关。然而，核因子红细胞 2 相关因子 2 (Nrf2) 途径是通过抑制氧化应激保护细胞免受 UVB 诱导损伤的关键因素。此外，Nrf2 的激活需要磷脂酰肌醇 3 激酶 (PI3K)/蛋白激酶 B (AKT) 途径的参与，该途径在各种细胞类型的存活中起主要作用。氢气对 UV 诱导的损伤具有保护作用，但潜在机制仍不清楚。本研究评估了氢气对 UVB 照射诱导的氧化应激损伤的保护作用，并探讨了其分子机制。在体外，收集 UVB 诱导的 HaCaT 细胞，通过荧光光谱法和 ELISA 检测活性氧、8-异前列腺素 F2α 和丙二醛；通过 MTT 和乳酸脱氢酶测定分别检测细胞活性和细胞毒性。此外，还通过 Western blot 等方法检测 PI3K、Akt、Nrf2 和血红素加氧酶-1 (HO-1) 的表达水平。所有结果表明，氢气降低了活性氧、8-异前列腺素 F2α 和丙二醛的水平，并促进了 PI3K、Akt、Nrf2 和血红素加氧酶-1 在 HaCaT 细胞中的 UVB 暴露诱导表达。值得注意的是，PI3K 抑制部分逆转了氢气对 UVB 诱导的 HaCaT 细胞的作用。因此，氢气通过抑制 Nrf2/HO-1 激活 PI3K/Akt 信号通路，有效保护细胞免受 UVB 辐射诱导的氧化应激。
