Department of Analytical Biochemistry, Institute of Food Technology and Nutrition, College of Natural Sciences, Rzeszow University, Rzeszow, Poland.
Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
Aging (Albany NY). 2020 Jan 21;12(2):1910-1927. doi: 10.18632/aging.102730.
The study was aimed at evaluation of the role of secondary oxidative stress in the stress-induced premature senescence (SIPS) of human fibroblasts induced by HO. Two fibroblast lines were used: lung MRC-5 and ear H8F2p25LM fibroblasts. The lines differed considerably in sensitivity to HO (IC of 528 and 33.5 μM, respectively). The cells were exposed to HO concentrations corresponding to IC and after 24 h supplemented with a range of antioxidants. Most of antioxidants studied slightly augmented the survival of fibroblasts at single concentrations or in a narrow concentration range, but the results were not consistent among the cell lines. Chosen antioxidants (4-amino-TEMPO, curcumin, caffeic acid and -coumaric acid) did not restore the level of glutathione decreased by HO. Hydrogen peroxide treatment did not induce secondary production of HO and even decreased it, decreased mitochondrial potential in both cell lines and induced changes in the mitochondrial mass inconsistent between the lines. Antioxidant protected mitochondrial potential only in H8F2p25LM cells, but attenuated changes in mitochondrial mass. These results speak against the intermediacy of secondary oxidative stress in the SIPS induced by HO and suggest that the small protective action of antioxidants is due to their effects on mitochondria.
本研究旨在评估次级氧化应激在 HO 诱导的人成纤维细胞应激性早衰（SIPS）中的作用。使用了两条成纤维细胞系：肺 MRC-5 和耳 H8F2p25LM 成纤维细胞。这两条系对 HO 的敏感性差异很大（IC 分别为 528 和 33.5 μM）。细胞暴露于相当于 IC 的 HO 浓度下，24 小时后用一系列抗氧化剂进行补充。研究中大多数抗氧化剂在单一浓度或狭窄浓度范围内略微提高了成纤维细胞的存活率，但结果在不同细胞系之间并不一致。选定的抗氧化剂（4-氨基-TEMPO、姜黄素、咖啡酸和阿魏酸）不能恢复 HO 降低的谷胱甘肽水平。过氧化氢处理不会诱导 HO 的次级产生，甚至会降低其水平，降低两条系中线粒体的潜能，并诱导线粒体质量的变化不一致。抗氧化剂仅在 H8F2p25LM 细胞中保护线粒体潜能，但减轻了线粒体质量的变化。这些结果表明，HO 诱导的 SIPS 中次级氧化应激的中间作用，并表明抗氧化剂的小保护作用是由于它们对线粒体的影响。
