title: Silibinin protects murine fibroblast L929 cells from UVB-induced apoptosis through the simultaneous inhibition of ATM-p53 pathway and autophagy.
abstract: Ultraviolet B (UVB) is a major cause of skin inflammation, leading to skin damage. Our previous in vivo study revealed that a natural flavonoid silibinin had marked anti-inflammatory effect on UVB-exposed murine skin. UVB exposure caused reduced autophagy in epidermis while it promoted autophagy in dermis. Nevertheless, silibinin inhibited the inflammatory flux in the skin epidermis as well as dermis through the modulation of autophagy. In order to elucidate the underlying protective mechanisms of silibinin for UVB damage on skin, separate studies on epidermis and dermis are helpful. Derived from the normal tissue of the mouse, L929 cells are capable of representing some characteristics of dermal cells. UVB irradiation caused L929 cell apoptosis in a time- and dose-dependent manner. Ataxia-telangiectasia-mutated (ATM) protein and p53 were activated to cause cell apoptosis, accompanying upregulation of the autophagic flux. The pharmacological inhibition of ATM, p53 and autophagy or the transfection with autophagy-associated protein-targeted small interfering RNAs showed that the UVB-activated ATM-p53 axis and autophagy formed a positive feedback loop, which synergistically promoted cell apoptosis. Silibinin treatment simultaneously repressed the activation of ATM-p53 and autophagy and thereby protected UVB-irradiated L929 cells from apoptotic death.
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Liaoning, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Liu
authors.forename: Wuxiyar
authors.initials: W
authors.lastname: Otkur
authors.forename: Yuning
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qiuyuan
authors.initials: Q
authors.lastname: Li
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Ye
authors.forename: Linghe
authors.initials: L
authors.lastname: Zang
authors.forename: Hao
authors.initials: H
authors.lastname: He
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hayashi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tashiro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Onodera
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikejima
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D064007:Ataxia Telangiectasia Mutated Proteins; D001343:Autophagy / Q000187:drug effects / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D025461:Feedback, Physiological; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D012838:Silymarin; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D000077385:Silybin; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: L929 cells; apoptosis; autophagy; silibinin; ultraviolet B (UVB)