UVB induces apoptosis via downregulation of CALML3-dependent JNK1/2 and ERK1/2 pathways in cataract

Jia,Yin; Qin,Qin; Fang,Chao‑Ping; Shen,Wei; Sun,Ting‑Ting; Huang,Yuan‑Lan; Li,Wen‑Jie; Deng,An‑Mei

doi:10.3892/ijmm.2018.3478

UVB induces apoptosis via downregulation of CALML3-dependent JNK1/2 and ERK1/2 pathways in cataract

Authors:
- Yin Jia
- Qin Qin
- Chao‑Ping Fang
- Wei Shen
- Ting‑Ting Sun
- Yuan‑Lan Huang
- Wen‑Jie Li
- An‑Mei Deng
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Affiliations: Department of Laboratory Diagnosis, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China, Department of Ophthalmology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China, Medical Department, The 455th Hospital of PLA, Shanghai 200052, P.R. China
Published online on: February 9, 2018 https://doi.org/10.3892/ijmm.2018.3478
Pages: 3041-3050

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Abstract

The aim of the current study was to understand the mechanisms of apoptosis occurring in cultured human lens epithelial cells (HLECs) following ultraviolet B (UVB) irradiation. The investigations intended to confirm the presence of apoptosis and to reveal the roles of oxidative stress, calcium (Ca2+), c‑Jun NH2‑terminal kinase (JNK)1/2, and extracellular signal‑regulated kinase (ERK)1/2 signaling pathway in these progresses. Cell apoptosis, ROS generation and intracellular Ca2+ concentration was measured by flow cytometry. The expression of CALML3, caspase-3, Bax, Bcl-2, p-JNK1/2, JNK1/2, p-ERK1/2 and ERK1/2 was measured by RT-qPCR and western blot analysis. Annexin V‑fluorescein isothiocyanate/propidium iodide staining demonstrated that UVB irradiation increased the apoptotic rate, reactive oxygen species (ROS) production and intracellular Ca2+ concentration of HLECs in dose‑ and time‑dependent manners. Overexpression of calmodulin like 3 (CALML3) reversed the effects of UVB irradiation on apoptosis, ROS production and Ca2+ concentration of HLECs, and decreased expressions of caspase‑3 and Bax, with increased expressions of Bcl‑2. Notably, silencing of CALML3 had similar effects to UVB irradiation and inhibited the activation JNK1/2 and ERK1/2 pathways. Nimodipine, a Ca2+‑channel antagonist, significantly attenuated the damages induced by CALML3 downregulation. In conclusion, UVB irradiation induced increase in apoptosis, ROS production and Ca2+ concentration of HLECs, in part, by downregulating the expression of CALML3 and involved oxidative stress, Ca2+, JNK1/2 and ERK1/2 signaling pathways, suggesting that investigating CALML3 may useful for developing cataract treatment.

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