Rotenone-induced apoptosis and role of calcium: a study on Neuro-2a cells

被引:0
|
作者
Supriya Swarnkar
Poonam Goswami
Pradeep Kumar Kamat
Sonam Gupta
Ishan K. Patro
Sarika Singh
Chandishwar Nath
机构
[1] CSIR-Central Drug Research Institute,Division of Toxicology
[2] CSIR-Central Drug Research Institute,Division of Pharmacology
[3] Jiwaji University,School of Studies in Neuroscience
来源
Archives of Toxicology | 2012年 / 86卷
关键词
Neuronal cells; Reactive oxygen species; Melatonin; Rotenone; DNA damage; Apoptosis;
D O I
暂无
中图分类号
学科分类号
摘要
Rotenone causes cytotoxicity in astrocytic cell culture by glial activation, which is linked to free radical generation. The present study is an investigation to explore whether rotenone could also cause cellular toxicity in mouse neuroblastoma cells (Neuro-2a) under treatment similar to astroglial cells. The effect of rotenone (0.1, 1, and 10 μM) on mitochondrial dehydrogenase enzyme activity by MTT reduction assay, PI uptake, total reactive oxygen species (ROS)/superoxide levels, nitrite levels, extent of DNA damage (by comet assay), and nuclear morphological alteration by Hoechst staining was studied. Caspase-3 and Ca2+/calmodulin-dependent protein kinase II (CaMKIIα) gene expression was determined to evaluate the apoptotic cell death and calcium kinase, respectively. Calcium level was estimated fluorometrically using fura-2A stain. Rotenone decreased mitochondrial dehydrogenase enzyme activity and generated ROS, superoxide, and nitrite. Rotenone treatment impaired cell intactness and nuclear morphology as depicted by PI uptake and chromosomal condensation of Neuro-2a cells, respectively. In addition, rotenone resulted in increased intracellular Ca+2 level, caspase-3, and CaMKIIα expression. Furthermore, co-exposure of melatonin (300 μM), an antioxidant to cell culture, significantly suppressed the rotenone-induced decreased mitochondrial dehydrogenase enzyme activity, elevated ROS and RNS. However, melatonin was found ineffective to counteract rotenone-induced increased PI uptake, altered morphological changes, DNA damage, elevated Ca+2, and increased expression of caspase-3 and CaMKIIα. The study indicates that intracellular calcium rather than oxidative stress is a major factor for rotenone-induced apoptosis in neuronal cells.
引用
收藏
页码:1387 / 1397
页数:10
相关论文
共 50 条
  • [41] Ethanol extract of Poria cocos induces apoptosis and differentiation in Neuro-2a neuroblastoma cells
    Jiang, Xia
    Xie, Jie
    Hu, Zhaotun
    Xiang, Xiaoliang
    BANGLADESH JOURNAL OF PHARMACOLOGY, 2022, 17 (04) : 105 - 113
  • [42] ROTENONE-INDUCED NEUROTOXICITY IN RAT BRAIN AREAS: A STUDY ON NEURONAL AND NEURONAL SUPPORTIVE CELLS
    Swarnkar, S.
    Goswami, P.
    Kamat, P. K.
    Patro, I. K.
    Singh, S.
    Nath, C.
    NEUROSCIENCE, 2013, 230 : 172 - 183
  • [43] Hydrogen Sulfide Inhibits Rotenone-Induced Apoptosis via Preservation of Mitochondrial Function
    Hu, Li-Fang
    Lu, Ming
    Wu, Zhi-Yuan
    Wong, Peter T. -H.
    Bian, Jin-Song
    MOLECULAR PHARMACOLOGY, 2009, 75 (01) : 27 - 34
  • [44] MITOSIS OF ROTENONE-INDUCED ENDOREDUPLICATION IN CHINESE-HAMSTER CELLS
    MATSUMOTO, K
    OHTA, T
    JAPANESE JOURNAL OF GENETICS, 1993, 68 (03): : 185 - 194
  • [45] Aluminum-maltolate induces apoptosis and necrosis in neuro-2a cells: Potential role for p53 signaling
    Johnson, VJ
    Kim, SH
    Sharma, RP
    TOXICOLOGICAL SCIENCES, 2005, 83 (02) : 329 - 339
  • [46] Preventive effects of Astaxanthin on rotenone-induced apoptosis and DJ-1 oxidation
    Tsuji, Shinji
    Satoh, Akira
    Ishikura, Masaharu
    Shimizu, Takahiko
    Shirasawa, Takuji
    NEUROSCIENCE RESEARCH, 2008, 61 : S122 - S122
  • [47] Inhibition of sphingomyelin synthase 1 affects ceramide accumulation and hydrogen peroxide-induced apoptosis in Neuro-2a cells
    Tu, Ranran
    Yang, Wei
    Hu, Zhiping
    NEUROREPORT, 2016, 27 (13) : 967 - 973
  • [48] Protective autophagy alleviates neurotoxin-gelsenicine induced apoptosis through PERK signaling pathway in Neuro-2a cells
    Li, Yujuan
    Hu, Peipei
    Zhang, Zhiqiang
    Yuan, Zhihang
    Yang, Kun
    Sun, Zhiliang
    TOXICOLOGY, 2022, 474
  • [49] Characterization of angiotensinergic responses in Neuro-2a cells
    Hoffmann, A
    Grunwald, WC
    Cool, DR
    FASEB JOURNAL, 2003, 17 (05): : A1057 - A1058
  • [50] PACAP and VIP Mitigate Rotenone-Induced Inflammation in BV-2 Microglial Cells
    Sarah Thomas Broome
    Giuseppe Musumeci
    Alessandro Castorina
    Journal of Molecular Neuroscience, 2022, 72 : 2163 - 2175