Oxidative Stress Defines the Neuroprotective or Neurotoxic Properties of Androgens in Immortalized Female Rat Dopaminergic Neuronal Cells

被引:57
|
作者
Holmes, Shaletha
Abbassi, Babak
Su, Chang
Singh, Meharvan
Cunningham, Rebecca L.
机构
[1] Univ N Texas, Dept Pharmacol & Neurosci, Ctr Focused Resources Her Hlth Educ & Res FOR HER, Inst Aging & Alzheimers Dis Res,Hlth Sci Ctr, Ft Worth, TX 76107 USA
[2] Univ N Texas, Cardiovasc Res Inst, Hlth Sci Ctr, Ft Worth, TX 76107 USA
基金
美国国家卫生研究院;
关键词
MEMBRANE TESTOSTERONE RECEPTORS; PARKINSONS-DISEASE; PERMEABILITY TRANSITION; ALZHEIMERS-DISEASE; CEREBRAL-ISCHEMIA; PROTEIN-KINASE; PROTEOLYTIC ACTIVATION; VASCULAR PARKINSONISM; 3-NITROPROPIONIC ACID; CORTICAL ASTROCYTES;
D O I
10.1210/en.2013-1242
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Males have a higher risk for developing Parkinson's disease and parkinsonism after ischemic stroke than females. Although estrogens have been shown to play a neuroprotective role in Parkinson's disease, there is little information on androgens' actions on dopamine neurons. In this study, we examined the effects of androgens under conditions of oxidative stress to determine whether androgens play a neuroprotective or neurotoxic role in dopamine neuronal function. Mitochondrial function, cell viability, intracellular calcium levels, and mitochondrial calcium influx were examined in response to androgens under both nonoxidative and oxidative stress conditions. Briefly, N27 dopaminergic cells were exposed to the oxidative stressor, hydrogen peroxide, and physiologically relevant levels of testosterone or dihydrotestosterone, applied either before or after oxidative stress exposure. Androgens, alone, increased mitochondrial function via a calcium-dependent mechanism. Androgen pretreatment protected cells from oxidative stress-induced cell death. However, treatment with androgens after the oxidative insult increased cell death, and these effects were, in part, mediated by calcium influx into the mitochondria. Interestingly, the negative effects of androgens were not blocked by either androgen or estrogen receptor antagonists. Instead, a putative membrane-associated androgen receptor was implicated. Overall, our results indicate that androgens are neuroprotective when oxidative stress levels are minimal, but when oxidative stress levels are elevated, androgens exacerbate oxidative stress damage.
引用
收藏
页码:4281 / 4292
页数:12
相关论文
共 50 条
  • [31] Glia Maturation Factor Dependent Inhibition of Mitochondrial PGC-1α Triggers Oxidative Stress-Mediated Apoptosis in N27 Rat Dopaminergic Neuronal Cells
    Selvakumar, Govindhasamy Pushpavathi
    Iyer, Shankar S.
    Kempuraj, Duraisamy
    Raju, Murugesan
    Thangavel, Ramasamy
    Saeed, Daniyal
    Ahmed, Mohammad Ejaz
    Zahoor, Harris
    Raikwar, Sudhanshu P.
    Zaheer, Smita
    Zaheer, Asgar
    MOLECULAR NEUROBIOLOGY, 2018, 55 (09) : 7132 - 7152
  • [32] Glia Maturation Factor Dependent Inhibition of Mitochondrial PGC-1α Triggers Oxidative Stress-Mediated Apoptosis in N27 Rat Dopaminergic Neuronal Cells
    Govindhasamy Pushpavathi Selvakumar
    Shankar S Iyer
    Duraisamy Kempuraj
    Murugesan Raju
    Ramasamy Thangavel
    Daniyal Saeed
    Mohammad Ejaz Ahmed
    Harris Zahoor
    Sudhanshu P. Raikwar
    Smita Zaheer
    Asgar Zaheer
    Molecular Neurobiology, 2018, 55 : 7132 - 7152
  • [33] Brimonidine is neuroprotective against glutamate-induced neurotoxicity, oxidative stress, and hypoxia in purified rat retinal ganglion cells
    Lee, Kelvin Yoon Chiang
    Nakayama, Mao
    Aihara, Makoto
    Chen, Yi-Ning
    Araie, Makoto
    MOLECULAR VISION, 2010, 16 (31-32): : 246 - 251
  • [34] Effects of propofol (PF) and sodium nitroprusside (SNP) during oxidative stress in rat neuronal and glial cells.
    Wojtczak, JA
    Sheu, SS
    ANESTHESIA AND ANALGESIA, 1999, 88 (02): : U245 - U245
  • [35] The neuroprotective effect of conditioned medium from neuronal and glial progenitor cells in H2O2-induced oxidative stress model
    Leonov, G.
    Salikhova, D.
    Bukharova, T.
    Efremova, A.
    Kiselev, S.
    Goldshtein, D.
    FEBS OPEN BIO, 2019, 9 : 232 - 232
  • [36] Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells
    Anantharam, Vellareddy
    Kaul, Siddharth
    Song, Chunjuan
    Kanthasamy, Arthi
    Kanthasamy, Anumantha G.
    NEUROTOXICOLOGY, 2007, 28 (05) : 988 - 997
  • [37] Docosahexaenoic Acid Attenuates Oxidative Stress-Induced Autophagy and Cell Death in Immortalized Adult Rat Schwann (IFRS1) Cells
    Tatsumi, Yasuaki
    Kato, Ayako
    Banno, Takahiro
    Niimi, Naoko
    Sango, Kazunori
    Himeno, Tatsuhito
    Kondo, Masaki
    Tsunekawa, Shin
    Kato, Yoshiro
    Kamiya, Hideki
    Nakamura, Jiro
    Kato, Koichi
    DIABETES, 2020, 69
  • [38] Investigations of oxidative stress, antioxidant response, and protein binding in chlorpyrifos exposed rat neuronal PC12 cells
    Geter, David R.
    Kan, H. Lynn
    Lowe, Ezra R.
    Rick, David L.
    Charles, Grantley D.
    Gollapudi, Bhaskar B.
    TOXICOLOGY MECHANISMS AND METHODS, 2008, 18 (01): : 17 - 23
  • [39] Evaluation of the neuroprotective potential of benzylidene digoxin 15 against oxidative stress in a neuroinflammation models induced by lipopolysaccharide and on neuronal differentiation of hippocampal neural precursor cells
    Cordeiro, Gilvania A.
    Faria, Jessica A.
    Pavan, Leticia
    Garcia, Israel J. P.
    Neves, Eduarda P. F. I.
    Lima, Gustavo Fernando de Frazao
    Campos, Hericles M.
    Ferreira, Pamela Y.
    Ghedini, Paulo C.
    Kawamoto, Elisa M.
    Lima, Maira C.
    Villar, Jose A. F. P.
    Orellana, Ana Maria M.
    Barbosa, Leandro A.
    Scavone, Cristoforo
    Leite, Jacqueline A.
    Santos, Herica L.
    FRONTIERS IN PHARMACOLOGY, 2025, 16
  • [40] Neuroprotective Effects of Papaya Epicarp Extract against Aluminum-Induced Oxidative Stress in Human Neuronal (SH-SY5Y) Cells
    Waly, Mostafa
    Guizani, Nejib
    Ali, Amanat
    Rahman, Mohammad Shafiur
    Deth, Richard
    FASEB JOURNAL, 2012, 26