Quercetin attenuates UV- and H(2)O(2)-induced decrease of collagen type I in cultured human lens epithelial cells.
Ultraviolet (UV) radiation is related to cataract formation. The dynamics of matrix proteins play crucial roles in cell proliferation, cell migration, and the remodeling of lens capsule and, possibly, cataract formation. However, the change of dynamics of matrix proteins, such as collagens, in lens cells in response to UV radiation has not been investigated. Using cultured human lens epithelial cells, we, for the first time, demonstrate that UV radiation induces a decrease of collagen type I in a time- and dose-dependent manner. Hydrogen peroxide (H(2)O(2)) also induces a collagen type I decrease in a similar pattern. We observed that UV and H(2)O(2) induce JNK and its downstream component, c-Jun, activation in both a time- and dose-dependent manner. The pharmacologic inhibitor of JNK or JNKi inhibits UV-induced JNK and c-Jun activation and attenuates a UV-induced decrease of collagen type I. Quercetin, a well known antioxidant, also protects against a UV- and H(2)O(2)-induced decrease of collagen type I in a dose-dependent manner. Quercetin inhibits UV- and H(2)O(2)-induced JNK and c-Jun activation. Collectively, we conclude that quercetin attenuates both a UV- and H(2)O(2)-induced decrease of collagen type I via the inhibiting of JNK/c-Jun activity. Understanding the cellular-signaling pathways involved in the UV- and H(2)O(2)-induced decrease of collagen type I may reveal potential therapeutic targets for the UV-induced cataract.
Jiang
Qin
Q
Department of Ophthalmology, Eye Hospital of Nanjing Medical University, Nanjing, China. jqin710@vip.sina.com
Cao
Cong
C
Zhou
Changlin
C
Song
Xiuzu
X
Healey
Sarah
S
Kouttab
Nicola
N
Chu
Wenming
W
Xu
Aier
A
Bi
Zhigang
Z
Wan
Yinsheng
Y
D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002386:Cataract / Q000209:etiology / Q000517:prevention & control; D002460:Cell Line; D024042:Collagen Type I / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects*; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects
D000975:Antioxidants; D024042:Collagen Type I; D011794:Quercetin; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases