Neurotoxic Effect of the Complex of the Ovine Prion Protein (OvPrPC) and RNA on the Cultured Rat Cortical Neurons

Liu, Meili; Wen, Jin; Xu, Xuefang; Zhao, Deming

doi:10.1007/s11064-011-0506-2

Cited by 4 publications

(4 citation statements)

References 35 publications

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“…12,17,18 A separate study indicates the neurotoxic effect found on the cultured rat cortical neurons of the complex of the ovine prion protein (OvPrP(C)) and RNA. 19,20 Besides, unique quadruplex structure and selective interaction of an RNA aptamer against bovine prion protein and may inhibits the prion disease propagation. 21 Understanding the processes of PrP C structural changes, viz.…”

Section: Introductionmentioning

confidence: 99%

Nucleic acid induced unfolding of recombinant prion protein globular fragment is pH dependent

Bera

Nandi

2014

Protein Science

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Nucleic acid can catalyze the conversion of a-helical cellular prion protein to b-sheet rich Proteinase K resistant prion protein oligomers and amyloid polymers in vitro and in solution. Because unfolding of a protein molecule from its ordered a-helical structure is considered to be a necessary step for the structural conversion to its b-sheet rich isoform, we have studied the unfolding of the a-helical globular 121-231 fragment of mouse recombinant prion protein in the presence of different nucleic acids at neutral and acid pH. Nucleic acids, either single or double stranded, do not have any significant effect on the secondary structure of the protein fragment at neutral pH; however the protein secondary structure is modified by the nucleic acids at pH 5. Nucleic acids do not show any significant effect on the temperature induced unfolding of the globular prion protein domain at neutral pH which, however, undergoes a gross conformational change at pH 5 as evidenced from the lowering of the midpoint of thermal denaturation temperatures, Tm, of the protein. The extent of Tm decrease shows a dependence on the nature of nucleic acid. The interaction of nucleic acid with the nonpolar groups exposed from the protein interior at pH 5 probably contributes substantially to the unfolding process of the protein.

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Section: Introductionmentioning

confidence: 99%

Nucleic acid induced unfolding of recombinant prion protein globular fragment is pH dependent

Bera

Nandi

2014

Protein Science

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“…11,22,28,29 The PrP−NA complex can also be toxic to cultured cells. 22,30 Knowing whether this effect is associated with specific nucleic acid sequences and/or structures would be enlightening. To answer this essential question, we started by asking whether different aggregation, stability, and toxicity effects are detected when different DNA sequences are tested.…”

mentioning

confidence: 99%

“…It has been observed that the interaction of PrP with nucleic acids is nonspecific because this protein binds several different RNA and DNA sequences in vitro. ,,, The PrP–NA complex can also be toxic to cultured cells. , Knowing whether this effect is associated with specific nucleic acid sequences and/or structures would be enlightening. To answer this essential question, we started by asking whether different aggregation, stability, and toxicity effects are detected when different DNA sequences are tested.…”

mentioning

confidence: 99%

Nonspecific Prion Protein–Nucleic Acid Interactions Lead to Different Aggregates and Cytotoxic Species

et al. 2012

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A misfolded form of the prion protein (PrP) is the primary culprit in mammalian prion diseases. It has been shown that nucleic acids catalyze the misfolding of cellular PrP into a scrapie-like conformer. It has also been observed that the interaction of PrP with nucleic acids is nonspecific and that the complex can be toxic to cultured cells. No direct correlation has yet been drawn between changes in PrP structure and toxicity due to nucleic acid binding. Here we asked whether different aggregation, stability, and toxicity effects are detected when nonrelated DNA sequences interact with recombinant PrP. Using spectroscopic techniques to analyze PrP tertiary and secondary structure and cellular assays to assess toxicity, we found that rPrP–DNA interactions lead to different aggregated species, depending on the sequence and size of the oligonucleotide tested. A 21-mer DNA sequence (D67) induced higher levels of aggregation and also dissimilar structural changes in rPrP, compared to binding to oligonucleotides with the same length and different nucleotide sequences or different GC contents. The rPrP–D67 complex induced significant cell dysfunction, which appears to be correlated with the biophysical properties of the complex. Although sequence specificity is not apparent for PrP–nucleic acid interactions, we believe that particular nucleic acid patterns, possibly related to GC content, oligonucleotide length, and structure, govern PrP recognition. Understanding the structural and cellular effects observed for PrP–nucleic acid complexes may shed light on the still mysterious pathology of the prion protein.

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“…After galanin treatment, cell viabilities were tested using a 3-(4,5-dimethylthiazole -2-yl)-2,5-diphenyl- tetrazolium bromide (MTT) assay [21], [22] Neuronal cell death was measured using a TdT-mediated biotin-dUTP nicked-end labeling (TUNEL) assay [23], [24], [25]. 4′-6-Diamidino-2-phenylindole (DAPI) was used to stain the nuclei of cultured cortical cells.…”

Section: Methodsmentioning

confidence: 99%

Galanin Protects against Nerve Injury after Shear Stress in Primary Cultured Rat Cortical Neurons

Liu

Song

et al. 2013

PLoS ONE

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The neuropeptide galanin and its receptors (GalR) are found to be up-regulated in brains suffering from nerve injury, but the specific role played by galanin remains unclear. This study aimed to explore the neuroprotective role of galanin after shear stress induced nerve injury in the primary cultured cortical neurons of rats. Our results demonstrated that no significant changes in cell death and viability were found after galanin treatment when subjected to a shear stress of 5 dyn/cm2 for 12 h, after increasing magnitude of shear stress to 10 dyn/cm2 for 12 h, cell death was significantly increased, while galanin can inhibit the nerve injury induced by shear stress with 10 dyn/cm2 for 12 h. Moreover, Gal2-11 (an agonist of GalR2/3) could also effectively inhibit shear stress-induced nerve injury of primary cultured cortical neurons in rats. Although GalR2 is involved in the galanin protection mechanism, there was no GalR3 expression in this system. Moreover, galanin increased the excitatory postsynaptic currents (EPSCs), which can effectively inhibit the physiological effects of shear stress. Galanin was also found to inhibit the activation of p53 and Bax, and further reversed the down regulation of Bcl-2 induced by shear stress. Our results strongly demonstrated that galanin plays a neuroprotective role in injured cortical neurons of rats.

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Neurotoxic Effect of the Complex of the Ovine Prion Protein (OvPrPC) and RNA on the Cultured Rat Cortical Neurons

Cited by 4 publications

References 35 publications

Nucleic acid induced unfolding of recombinant prion protein globular fragment is pH dependent

Nucleic acid induced unfolding of recombinant prion protein globular fragment is pH dependent

Nonspecific Prion Protein–Nucleic Acid Interactions Lead to Different Aggregates and Cytotoxic Species

Galanin Protects against Nerve Injury after Shear Stress in Primary Cultured Rat Cortical Neurons

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