UVB induces apoptosis via downregulation of CALML3-dependent JNK1/2 and ERK1/2 pathways in cataract
Open accessAbstract
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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CALML3 silencing led to increased apoptosis accompanied by a decreased activation of ERK1/2 and JNK.
“Calmodulin like 3 (CALML3) silencing led to increased apoptosis accompanied by a decreased activation of ERK1/2 and JNK [ 209 ]”
From MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges (2023) · cites this paper as [209]
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Neves, V. C. M., Satie Okajima, L., Elbahtety, E., Joseph, S., Daly, J., Menon, A., Fan, D., Volkyte, A., Mainas, G., Fung, K., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26619244
Nadeb, M., Aghaei, S. S., Komeili-Movahed, T., & Afkhami, H. (2026) · Oxidative Medicine and Cellular Longevity · doi:10.1155/omcl/5525367
- Authors
- Jia, Y., Qin, Q., Fang, C., Shen, W., Sun, T., Huang, Y., Li, W., & Deng, A.
- Affiliations
- Second Military Medical University (CN)
- Department of Laboratory Diagnosis, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China
- Medical Department, The 455th Hospital of PLA, Shanghai 200052, P.R. China
- Venue
- International Journal of Molecular Medicine
- Publisher
- Spandidos Publications
- Published
- 2018-02-09
- Volume
- 41
- Issue
- 5
- Pages
- 3041-3050
- ISSN
- 1107-3756 (ISSN-L)
- 1791-244X
- OpenAlex
- W2787909527
- Cited by
- 31
- References
- 36
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 11 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 4
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (BWS14J023, 81471605, 81170834, 81273282, 81202353)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
- Keywords
- UVB irradiation, cataract, lens epithelial cells, apoptosis, JNK1/2 signaling, ERK signaling, reactive oxygen species, oxidative stress, intracellular calcium, caspase-3, Bax/Bcl-2 ratio, nimodipine, calcium channel blockers
- MeSH terms
- Calmodulin, Cataract, Cells, Cultured, Humans, Lens, Crystalline, Ultraviolet Rays, Down-Regulation, Apoptosis, Oxidative Stress, MAP Kinase Signaling System
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