Analysis of age dependent changes of Topoisomerase II α and β in rat brain

Kondapi, Anand K.; Mulpuri, Neelima; Mandraju, Raj Kumar; Sasikaran, B.; Rao, K. S.

doi:10.1016/j.ijdevneu.2003.10.006

Cited by 36 publications

(26 citation statements)

References 21 publications

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“…A recent report also reveals that TOP IIβ is associated with genomic instability in the cerebella region of aging brain [40]. TOP IIβ is treated as an additional biomarker in DNA repair and aging using cultured cerebella granule neurons as an in vitro aging model [41].…”

Section: Discussionmentioning

confidence: 99%

Nurr1 regulates Top IIβ and functions in axon genesis of mesencephalic dopaminergic neurons

Heng

Jin

Zhang

et al. 2012

Mol Neurodegeneration

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BackgroundNURR1 (also named as NR4A2) is a member of the steroid/thyroid hormone receptor family, which can bind to DNA and modulate expression of target genes. Previous studies have shown that NURR1 is essential for the nigral dopaminergic neuron phenotype and function maintenance, and the defects of the gene are possibly associated with Parkinson's disease (PD).ResultsIn this study, we used new born Nurr1 knock-out mice combined with Affymetrix genechip technology and real time polymerase chain reaction (PCR) to identify Nurr1 regulated genes, which led to the discovery of several transcripts differentially expressed in the nigro-striatal pathway of Nurr1 knock-out mice. We found that an axon genesis gene called Topoisomerase IIβ (Top IIβ) was down-regulated in Nurr1 knock-out mice and we identified two functional NURR1 binding sites in the proximal Top IIβ promoter. While in Top IIβ null mice, we saw a significant loss of dopaminergic neurons in the substantial nigra and lack of neurites along the nigro-striatal pathway. Using specific TOP II antagonist ICRF-193 or Top IIβ siRNA in the primary cultures of ventral mesencephalic (VM) neurons, we documented that suppression of TOP IIβ expression resulted in VM neurites shortening and growth cones collapsing. Furthermore, microinjection of ICRF-193 into the mouse medial forebrain bundle (MFB) led to the loss of nigro-striatal projection.ConclusionTaken together, our findings suggest that Top IIβ might be a down-stream target of Nurr1, which might influence the processes of axon genesis in dopaminergic neurons via the regulation of TOP IIβ expression. The Nurr1-Top IIβ interaction may shed light on the pathologic role of Nurr1 defect in the nigro-striatal pathway deficiency associated with PD.

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Section: Discussionmentioning

confidence: 99%

Nurr1 regulates Top IIβ and functions in axon genesis of mesencephalic dopaminergic neurons

Heng

Jin

Zhang

et al. 2012

Mol Neurodegeneration

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“…The activity of Top II is the highest in "Young" rat brain, moderate in "Adult" brain and the lowest in "Old" brain. The protein level of Top II correlates well with its enzymatic activity, suggesting that the enzymatic activity and protein level of Top II are high in young brain, and these levels decrease with the increase of age [17] .…”

Section: Top Iimentioning

confidence: 86%

拓扑异构酶IIβ在神经发育中的作用

Heng

2010

Neurosci. Bull.

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Type II DNA topoisomerases (Tops) are ATP-dependent enzymes that catalyze topological transformations of genomic DNA by the transport of one DNA double helix through another. In mammals, there are 2 isoforms of DNA Top II, termed Top IIα and Top IIβ. The IIβ isoform is abundantly expressed in cells that have undergone the final cell division and are committed to differentiation into neuronal cells. In recent years, there have been accumulating studies showing the significant role of Top IIβ in neuronal development through regulating expression of certain genes in cells committed to the neuronal fate after the final division. These genes are involved in the processes of neuronal differentiation, migration, axon guidance and so on. The present review mainly focused on the research progress on the role of Top IIβ in neuronal development over the recent decades.

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“…11,44 Involvement of Topo-2β in repair initiation complexes 54 and nonhomologous end joining reported existing. Furthermore, Topo-2β is associated with genomic instability in the cerebellar region of the aging brain and the decreasing activity of Topo-2β in aging neurons 41,42 reveals its possible role in DNA repair activity. Furthermore, Topo-2β is associated with genomic instability in the cerebellar region of the aging brain and the decreasing activity of Topo-2β in aging neurons 41,42 reveals its possible role in DNA repair activity.…”

Section: Discussionmentioning

confidence: 99%

“…20 Statistical analysis of cell viability of ATRA-treated and untreated SK-N-SH cells were performed using GraphPad Prism 7.0 trial software. 41,42 Downregulation of protein expression in the cancer cells may be due to the genetic mutation in the genes involved in neuronal differentiation at later stages. Numerous changes in the membrane, cytoplasm, and nucleus have been reported in the ATRA-induced differentiation.…”

Section: Discussionmentioning

confidence: 99%

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Status of topoisomerase‐2β protein in all‐trans retinoic acid–treated human neuroblastoma (SK‐N‐SH) cells

Bhanothu

Kondapi

2018

J of Cellular Biochemistry

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Of the mammalian topoisomerase (Topo)‐2 isozymes (α and β), Topo‐2β protein has been reported to regulate neuronal development and differentiation. However, the status of Topo‐2β in all‐trans retinoic acid (ATRA)‐treated human neuroblastoma (SK‐N‐SH) cells is not understood. More information about the effects of ATRA on SK‐N‐SH cells is needed to reveal the role of ATRA in the regulation of Topo‐2β levels and spontaneous regression of SK‐N‐SH cells to predict the clinical activity. This study was proposed to investigate the status and role of Topo‐2β protein in ATRA‐induced survival and neuronal differentiation of SK‐N‐SH cells. Microscopic, sodium dodecyl sulfate polyacrylamide gel electrophoresis after immunoprecipitations and Western blot analysis were used to study and compare Topo‐2β protein among 10 µM ATRA‐treated SK‐N‐SH cells and controls at different time points. The level of Topo‐2β protein increased in the initial days of treatment but markedly decreased upon induction of differentiation by ATRA in later stages. Upon ATRA treatment, SK‐N‐SH cells stretched, exhibited neurite extensions, and acquired a neuronal phenotype. Both treated and untreated SK‐N‐SH cells were able to migrate, occupy the scratched area, and completely recolonized 24 hours later. These results suggest an indirect role of Topo‐2β protein in regulation of genes involved in cell migration and differentiation of ATRA‐treated SK‐N‐SH cells. This study suggests that Topo‐2β may be part of activation/repression of protein complexes activated by epigenetic modifying agents, differentiating signals, and inducible locus. However, detailed studies are needed to explore the ATRA‐downstream genes leading to Topo‐2β regulation and regulatory proteins of neuronal differentiation.

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Analysis of age dependent changes of Topoisomerase II α and β in rat brain

Cited by 36 publications

References 21 publications

Nurr1 regulates Top IIβ and functions in axon genesis of mesencephalic dopaminergic neurons

Nurr1 regulates Top IIβ and functions in axon genesis of mesencephalic dopaminergic neurons

拓扑异构酶IIβ在神经发育中的作用

Status of topoisomerase‐2β protein in all‐trans retinoic acid–treated human neuroblastoma (SK‐N‐SH) cells

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