Structure, Dynamics, and Membrane Topology of Stannin: A Mediator of Neuronal Cell Apoptosis Induced by Trimethyltin Chloride

Buck‐Koehntop, Bethany A.; Mascioni, Alessandro; Buffy, Jarrod J.; Veglia, Gianluigi

doi:10.1016/j.jmb.2005.09.038

Cited by 48 publications

(36 citation statements)

References 87 publications

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“…This is not surprising, as it is reasonably because of the different model used (transformed cell line in vitro vs. hippocampal lesions in vivo), based on different methodologies (Affymetrix expression array covering over 15.866 transcripts vs. Atlas membrane arrays representing 1176 genes) and experimental conditions along with different species (rat vs. mouse). In addition, there are some differences between the results here reported and the common molecular alterations described by other Authors in TMT toxicity models (mainly based on neuronal cultures or selected brain sections), such as caspases activation, stannin overexpression and the involvement of common signal transduction pathways (Pavlakovic et al 1995;Kane et al 1998;Gunasekar et al 2001;Jenkins and Barone 2004;Buck-Koehntop et al 2005). This could be likely related to the inherent differences between un-primed PC12 cells and primary neuronal cultures or hippocampal sections, which are commonly used to describe the neuro-specific effects of TMT.…”

Section: Discussioncontrasting

confidence: 73%

Hypoxia‐like transcriptional activation in TMT‐induced degeneration: microarray expression analysis on PC12 cells

Lattanzi¹,

Bernardini²,

Gangitano³

et al. 2006

Journal of Neurochemistry

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To more clearly elucidate the complete network of molecular mechanisms induced by trimethyltin (TMT) toxicity, we used a homogeneous cell culture model represented by PC12 cells treated with 1 and 5 lmol/L TMT for 24 h. The gene expression profile was performed by microarray analysis, enabling us to identify 189 genes that were significantly modulated in treated cells, compared with controls. The main effects of TMT on gene expression seem to be related to the activation of metabolic processes (glycolysis and lipogenesis) along with cell death pathways, membrane remodeling and intracellular biomolecules trafficking. These alterations are triggered by the neurotoxicant earlier than a strong decrease in cell viability, which occurs at higher TMT concentrations or at later time points. Some aspects of the transcriptional modulation observed in this study resemble the gene activation known to occur during cell response to hypoxia. Other cell toxicants have also been reported to exert similar effects on gene expression. Therefore, our data help to delineate general basic adaptive mechanisms possibly shared by cells responding to different death-inducing noxae, such as TMT.

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Section: Discussioncontrasting

confidence: 73%

Hypoxia‐like transcriptional activation in TMT‐induced degeneration: microarray expression analysis on PC12 cells

Lattanzi¹,

Bernardini²,

Gangitano³

et al. 2006

Journal of Neurochemistry

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“…63 The SNN gene encodes the stannin protein, a highly conserved, 88-amino acid small protein. 64 WNK1, also known as WNK lysine deficient protein kinase 1, encodes a cytoplasmic serine-threonine kinase that is expressed in the distal nephron. 65 The ABCA1 gene encodes ATP-binding cassette transporter ABCA1, which is a major regulator of cellular cholesterol and phospholipid homeostasis.…”

Section: Resultsmentioning

confidence: 99%

Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene

Luo

Huang

et al. 2013

Mol Psychiatry

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“…Under these two conditions, the pattern of NOE peaks for each residue is identical in both number and intensity of the NOE cross-peaks, confirming that the protein fold is not affected by the presence of the micelle and the lipid anchor. We titrated the lipidated rLP2086-B01 with the paramagnetic reagent 5-doxyl stearic acid, which reconstitutes into the micelle, inducing selective paramagnetic broadening of residues bound to the micellar surface (33,34). With the exception of Cys 1 and Gly 2 (supplemental Fig.…”

Section: Solution Structure Of the Nonlipidated Lp2086 Variant B01-mentioning

confidence: 99%

Structural Basis for the Immunogenic Properties of the Meningococcal Vaccine Candidate LP2086

Mascioni

Bentley

Camarda

et al. 2009

Journal of Biological Chemistry

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LP2086 is a family of outer membrane lipoproteins fromNeisseria meningitidis, which elicits bactericidal antibodies and are currently undergoing human clinical trials in a bivalent formulation where each antigen represents one of the two known LP2086 subfamilies. Here we report the NMR structure of the recombinant LP2086 variant B01, a representative of the LP2086 subfamily B. The structure reveals a novel fold composed of two domains: a "taco-shaped" N-terminal ␤-sheet and a C-terminal ␤-barrel connected by a linker. The structure in micellar solution is consistent with a model of LP2086 anchored to the outer membrane bilayer through its lipidated N terminus. A long flexible chain connects the folded part of the protein to the lipid anchor and acts as spacer, making both domains accessible to the host immune system. Antibodies broadly reactive against members from both subfamilies have been mapped to the N terminus. A surface of subfamily-defining residues was identified on one face of the protein, offering an explanation for the induction of subfamily-specific bactericidal antibodies.Neisseria meningitidis is a Gram-negative bacterial pathogen, which colonizes the upper respiratory tract, occasionally invading the bloodstream, causing sepsis, and crossing the blood-brain barrier, resulting in meningitis. Despite the availability of effective antibiotic treatment, the rapid progression of meningococcal disease still results in substantial morbidity and mortality (1). Five meningococcal serogroups, categorized according to the chemical structure of the bacterial capsular polysaccharides, A, B, C, Y, and W135, account for most of the disease (2). Although a vaccine against four of the five major serogroups of meningococci is currently available, a vaccine for the prevention of serogroup B disease is still an unmet clinical need (3). The development of vaccines against serogroup B meningococci has focused on subcapsular antigens, in order to avoid the risk of autoimmunity arising from structural similarities between the capsular polysaccharides and the sialic acidmodified surface of developing human brain (1,4,5).Recently, a new family of lipidated outer membrane proteins, LP2086, was identified as a potential vaccine target (6). Members of the LP2086 family have been divided into two subfamilies, subfamily A and B, based on their genetic variation (6, 7). Since recombinant LP2086 (rLP2086) 3 elicits a bactericidal response that is largely subfamily-specific, a bivalent vaccine containing one protein from each subfamily will offer protection against serogroup B meningococci (6, 8 -11). LP2086 lipoproteins are lipidated at the N-terminal Cys with a tripalmitoyl lipid tail, which anchors the protein to the bacterial membrane (12). More recently, LP2086 was found to induce serum resistance via binding with human Factor H, a key regulator of the alternative complement pathway that prevents autologous complement attack (13).Our work seeks to understand the structural elements of LP2086 responsible for inducing the subf...

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Structure, Dynamics, and Membrane Topology of Stannin: A Mediator of Neuronal Cell Apoptosis Induced by Trimethyltin Chloride

Cited by 48 publications

References 87 publications

Hypoxia‐like transcriptional activation in TMT‐induced degeneration: microarray expression analysis on PC12 cells

Hypoxia‐like transcriptional activation in TMT‐induced degeneration: microarray expression analysis on PC12 cells

Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene

Structural Basis for the Immunogenic Properties of the Meningococcal Vaccine Candidate LP2086

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