title: Inhibition of Cartilage Acidic Protein 1 Reduces Ultraviolet B Irradiation Induced-Apoptosis through P38 Mitogen-Activated Protein Kinase and Jun Amino-Terminal Kinase Pathways.
abstract: OBJECTIVE
  Ultraviolet B (UVB) irradiation can easily induce apoptosis in human lens epithelial cells (HLECs) and further lead to various eye diseases including cataract. Here for the first time, we investigated the role of cartilage acidic protein 1 (CRTAC1) gene in UVB irradiation induced-apoptosis in HLECs.
  
  
  METHODS
  Three groups of HLECs were employed including model group, empty vector group, and CRTAC1 interference group.
  
  
  RESULTS
  After UVB irradiation, the percentage of primary apoptotic cells was obviously fewer in CRTAC1 interference group. Meanwhile, inhibition of CRTAC1 also reduced both reactive oxygen species (ROS) production and intracellular Ca2+ concentration, but the level of mitochondrial membrane potential (Δψm) was increased in HLECs. Further studies indicated that superoxide dismutase (SOD) activity and total antioxidative (T-AOC) level were significantly increased in CRTAC1-inhibited cells, while the levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) were significantly decreased. ELISA analysis of CRTAC1-inhibited cells showed that the concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly decreased, but the concentration of interleukin-10 (IL-10) was significantly increased. Western blot analyses of eight apoptosis-associated proteins including Bax, Bcl-2, p38, phospho-p38 (p-p38), Jun amino-terminal kinases (JNK1/2), phospho-JNK1/2 (p-JNK1/2), calcium-sensing receptor (CasR), and Ca2+/calmodulin-dependent protein kinase II (CaMKII) indicated that the inhibition of CRTAC1 alleviated oxidative stress and inflammation response, inactivated calcium-signaling pathway, p38 and JNK1/2 signal pathways, and eventually reduced UVB irradiation induced-apoptosis in HLECs.
  
  
  CONCLUSIONS
  These results provided new insights into the mechanism of cataract development, and demonstrated that CRTAC1 could be a potentially novel target for cataract treatment.
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Key Laboratory of Myopia of State Health Ministry, and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai, China.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Ji
authors.forename: Xianfang
authors.initials: X
authors.lastname: Rong
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.forename: Jun
authors.initials: J
authors.lastname: Rao
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000528:radiation effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism* / Q000528:radiation effects; D005434:Flow Cytometry; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000528:radiation effects*; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C422245:CRTAC1 protein, human; D002135:Calcium-Binding Proteins; D016207:Cytokines; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium