Effect of fluoride exposure on mRNA expression of cav1.2 and calcium signal pathway apoptosis regulators in PC12 cells |
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| Institution: | 1. College of Chemistry and Life Science at Zhejiang Normal University, Jinhua, Zhejiang, 321004, PR China;2. College of Sports and Health Science, Zhejiang Normal University, Jinhua, Zhejiang, 321004, PR China;3. College of Xing Zhi, Zhejiang Normal University, Jinhua, Zhejiang, 321004, PR China;1. The Dr. Janusz Daab Hospital of Trauma Surgery in Piekary Śląskie, Poland;2. The Jan Grodek Higher Vocational State School in Sanok, Medical Institute, Poland;3. Department of Environmental Health and Epidemiology, Institute of Occupational Medicine in Sosnowiec, Poland;4. Chair and Department of Toxicology, Silesian Medical University of Katowice, Faculty of Pharmacy in Sosnowiec, Poland;5. Department of Toxicology and Health Protection, Medical University of Silesia, Katowice, Poland;6. Department of Pediatrics in Zabrze, Medical University of Silesia in Katowice, Poland;1. Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil;2. Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, San Francisco, USA;3. Department of Morphophysiological Sciences, State University of Maringá, Maringá, Brazil;1. Department of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China;2. Department of Emergency, The First People’s Hospital of Zhangjiagang, Suzhou, China;3. Department of Intensive Care Unit, The First People’s Hospital of Zhangjiagang, Suzhou, China;4. Department of Orthopedics, The First People’s Hospital of Zhangjiagang, Suzhou, China;5. Department of Neurosurgery and Translational Medicine Center, The First People’s Hospital of Zhangjiagang, Suzhou, China;6. Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China;2. Department of Medicine, Brigham and Women''s Hospital, Biomaterials Innovation Research Center, Harvard Medical School, Cambridge, MA 02139, USA;3. Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran;4. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran;5. Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran;11. Department of Pathology, Tehran University of Medical sciences (TUMS), Tehran, Iran |
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| Abstract: | This study investigated the effects of fluoride exposure on the mRNA expression of Cav1.2 calcium signaling pathway and apoptosis regulatory molecules in PC12 cells. The viability of PC12 cell receiving high fluoride (5.0 mM) and low fluoride (0.5 mM) alone or fluoride combined with L-type calcium channel (LTCC) agonist/inhibitor (5 umol/L FPL6417/2 u mol/L nifedipine) was detected using cell counting kit-8 at different time points (2, 4, 6, 8, 12, 10, and 24 h). Changes in the cell configuration were observed after exposing the cells to fluoride for 24 h. The expression levels of molecules related to the LTCC were examined, particularly, Cav1.2, c-fos, CAMK II, Bax, and Bcl-2. Fluoride poisoning induced severe cell injuries, such as decreased PC12 cell activity, enhanced cell apoptosis, high c-fos, CAMKII, and Bax mRNA expression levels. Bcl-2 expression level was also reduced. Meanwhile, high fluoride, high fluoride with FPL64176, and low fluoride with FPL64176 enhanced the Cav1.2 expression level. In contrast, low fluoride, high fluoride with nifedipine, and low fluoride with nifedipine reduced the Cav1.2 expression level. Thus, Cav1.2 may be an important molecular target for the fluorosis treatment, and the LTCC inhibitor nifedipine may be an effective drug for fluorosis. |
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| Keywords: | Fluoride exposure PC12 cell L-type calcium channel CAMKII Cell apoptosis |
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