Recombinant Klotho Protects Human Periodontal Ligament Stem Cells by Regulating Mitochondrial Function and the Antioxidant System during H2O2-Induced Oxidative Stress
Autor: | Xuefeng Lin, Xiaojun Huang, Xiayi Wu, Huan Chen, Chuanqiang Fu, Yan Wang, Yingying Peng |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Aging
Article Subject Periodontal ligament stem cells Periodontal Ligament medicine.disease_cause urologic and male genital diseases Biochemistry Antioxidants Phosphatidylinositol 3-Kinases Oxygen Consumption Osteogenesis medicine Humans lcsh:QH573-671 Protein kinase B Cell damage Klotho Klotho Proteins PI3K/AKT/mTOR pathway Cells Cultured Glucuronidase lcsh:Cytology Chemistry Forkhead Box Protein O1 Guided Tissue Regeneration Superoxide Dismutase Stem Cells Cell Biology General Medicine Hydrogen Peroxide medicine.disease female genital diseases and pregnancy complications Recombinant Proteins Cell biology Mitochondria Transplantation Oxidative Stress Stem cell Proto-Oncogene Proteins c-akt Oxidative stress Research Article Signal Transduction |
Zdroj: | Oxidative Medicine and Cellular Longevity Oxidative Medicine and Cellular Longevity, Vol 2019 (2019) |
ISSN: | 1942-0994 1942-0900 |
Popis: | Human periodontal ligament stem cells (hPDLSCs) are a favourable source for tissue engineering, but oxidative stress conditions during cell culture and transplantation could affect stem cell viability and stemness, leading to failed regeneration. The aim of this study was to evaluate the antioxidant and protective effects of Klotho, an antiageing protein, against cell damage and the loss of osteogenesis in hPDLSCs in H2O2-induced oxidative environments. H2O2 was used as an exogenous reactive oxygen species (ROS) to induce oxidative stress. Recombinant human Klotho protein was administered before H2O2 treatment. Multitechniques were used to assess antioxidant activity, cell damage, and osteogenic ability of hPDLSCs in oxidative stress and the effects of Klotho on hPDLSCs. Mitochondrial function was analyzed by an electron microscopy scan of cellular structure, mitochondrial DNA copy number, and cellular oxygen consumption rate (OCR). Furthermore, we explored the pathway by which Klotho may function to regulate the antioxidant system. We found that pretreatment with recombinant human Klotho protein could enhance SOD activity and reduce intracellular oxidative stress levels. Klotho reduced H2O2-induced cellular damage and eventually maintained the osteogenic differentiation potential of hPDLSCs. Notably, Klotho promoted mitochondrial function and activated antioxidants by negatively regulating the PI3K/AKT/FoxO1 pathway. The findings suggest that Klotho protein enhanced the antioxidative ability of hPDLSCs and protected stem cell viability and stemness from H2O2-induced oxidative stress by restoring mitochondrial functions and the antioxidant system. |
Databáze: | OpenAIRE |
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