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Silibinin protects murine fibroblast L 929 cells from UVB ‐induced apoptosis through the simultaneous inhibition of ATM ‐p53 pathway and autophagy
Author(s) -
Liu Weiwei,
Otkur Wuxiyar,
Zhang Yuning,
Li Qiuyuan,
Ye Yuanchao,
Zang Linghe,
He Hao,
Hayashi Toshihiko,
Tashiro Shinichi,
Onodera Satoshi,
Ikejima Takashi
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12426
Subject(s) - silibinin , autophagy , apoptosis , dermis , microbiology and biotechnology , epidermis (zoology) , chemistry , dermal fibroblast , programmed cell death , fibroblast , downregulation and upregulation , cancer research , biology , biochemistry , in vitro , anatomy , gene
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, L 929 cells are capable of representing some characteristics of dermal cells. UVB irradiation caused L 929 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 RNA s 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 L 929 cells from apoptotic death.