Mass spectrometric identification of formaldehyde-induced peptide modifications under in vivo protein cross-linking conditions

Toews, Judy; Rogalski, Jason C.; Clark, Tom; Kast, Juergen

doi:10.1016/j.aca.2008.04.049

Cited by 117 publications

(101 citation statements)

References 19 publications

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“…An analogous study has shown that ethanol inhibits LTP formation by blocking the NMDA receptor, possibly because the cysteine residues of NR2B are sensitive to ethanol (Herin et al 2001), and leads to amnesia (Brioni et al 1989;Dildy and Leslie 1989;Tokuda et al 2007;Wirkner et al 1999). Some studies have shown that formaldehyde can spontaneously modify the cysteine residues of proteins (Metz et al 2006;Toews et al 2008). We therefore hypothesized that formaldehyde may modify the cysteine residues of NR1 or NR2B, although the specific residues involved need further investigation.…”

Section: Discussionmentioning

confidence: 95%

Accumulated hippocampal formaldehyde induces age-dependent memory decline

Tong

Han

Luo

et al. 2012

AGE

187

151

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Aging is an important factor in memory decline in aged animals and humans and in Alzheimer's disease and is associated with the impairment of hippocampal long-term potentiation (LTP) and downregulation of NR1/NR2B expression. Gaseous formaldehyde exposure is known to induce animal memory loss and human cognitive decline; however, it is unclear whether the concentrations of endogenous formaldehyde are elevated in the hippocampus and how excess formaldehyde affects LTP and memory formation during the aging process. In the present study, we report that hippocampal formaldehyde accumulated in memorydeteriorating diseases such as age-related dementia. Spatial memory performance was gradually impaired in normal Sprague-Dawley rats by persistent intraperitoneal injection with formaldehyde. Furthermore, excess formaldehyde treatment suppressed the hippocampal LTP formation by blocking N-methyl-D-aspartate (NMDA) receptor. Chronic excess formaldehyde treatment over a period of 30 days markedly decreased the viability of the hippocampus and down-regulated the expression of the NR1 and NR2B subunits of the NMDA receptor. Our results indicate that excess endogenous formaldehyde is a critical factor in memory loss in age-related memory-deteriorating diseases.

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Section: Discussionmentioning

confidence: 95%

Accumulated hippocampal formaldehyde induces age-dependent memory decline

Tong

Han

Luo

et al. 2012

AGE

187

151

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“…At ambient temperature, formaldehyde forms predominantly immonium cations that are reactive toward nucleophiles, such as the N terminus of a protein and the lateral chains of cysteine, lysine, histidine, and tyrosine residues (14). Formaldehyde is ideal to detect specific protein-protein interactions due to (i) a short reaction time that minimizes nonspecific cross-linking, (ii) the formation of highly reactive intermediates that allow fixation of transient interactions, and (iii) a short cross-linking distance (ϳ0.2-0.3 nm) (15).…”

mentioning

confidence: 99%

Avirulence Protein 3a (AVR3a) from the Potato Pathogen Phytophthora infestans Forms Homodimers through Its Predicted Translocation Region and Does Not Specifically Bind Phospholipids

Wawra

Agacan

Boddey

et al. 2012

Journal of Biological Chemistry

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Background: AVR3a is a Phytophthora infestans effector that translocates into potato cells dependent on the N-terminal RxLR leader. Results: AVR3a dimerization is inhibited by a mutation that also impairs translocation. Conclusion: Phospholipid binding of AVR3a is probably physiologically irrelevant because only denatured protein molecules bind. Significance: Our findings will help us to understand how oomycete RxLR effectors function.

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“…From these, a total of 486 N termini were shared between both preservation methods (among all replicates of cryopreserved and FFPE tissues, respectively). Previous studies indicate that proteins extracted from FFPE tissues are susceptible to a ϩ12 Da addition at N termini, lysine, tryptophan, tyrosine, serine, and threonine residues, as well as a ϩ30 Da addition at cysteine, histidine, lysine, and arginine residues (20,33,34). In both cryopreserved and FFPE samples, the fraction of peptides displaying these modifications remained below the 5% false discovery rate (data not shown).…”

Section: Enrichment Of N-terminal Peptides From Ffpe Specimens-mentioning

confidence: 94%

“…Three biological replicates were investigated in combination with a label-switch between 12 COH 2 formaldehyde and 13 COD 2 formaldehyde to provide statistical significance. Statistical analysis using linear models for microarray data (Limma) (20,21) allows for the use of linear models to assess differential expression in the context of multifactor designed experiments. In addition, Limma has the ability to analyze complex experiments involving comparisons between many peptides simultaneously in a small sample size.…”

Section: Methodsmentioning

confidence: 99%

Formalin-Fixed, Paraffin-Embedded Tissues (FFPE) as a Robust Source for the Profiling of Native and Protease-Generated Protein Amino Termini

Lai

Weißer

Nilse

et al. 2016

Molecular & Cellular Proteomics

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Dysregulated proteolysis represents a hallmark of numerous diseases. In recent years, increasing number of studies has begun looking at the protein termini in hope to unveil the physiological and pathological functions of proteases in clinical research. However, the availability of cryopreserved tissue specimens is often limited. Alternatively, formalin-fixed, paraffin-embedded (FFPE) tissues offer an invaluable resource for clinical research. Pathologically relevant tissues are often stored as FFPE, which represent the most abundant resource of archived human specimens. In this study, we established a robust workflow to investigate native and protease-generated protein N termini from FFPE specimens. We demonstrate comparable N-terminomes of cryopreserved and formalin-fixed tissue, thereby showing that formalin fixation/paraffin embedment does not proteolytically damage proteins. Accordingly, FFPE specimens are fully amenable to N-terminal analysis. Moreover, we demonstrate feasibility of FFPE-degradomics in a quantitative N-terminomic study of FFPE liver specimens from cathepsin L deficient or wild-type mice. Using a machine learning approach in combination with the previously determined cathepsin L specificity, we successfully identify a number of potential cathepsin L cleavage sites. Our study establishes FFPE specimens as a valuable alternative to cryopreserved tissues for degradomic studies. Molecular & Cellular Proteomics 15:

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Mass spectrometric identification of formaldehyde-induced peptide modifications under in vivo protein cross-linking conditions

Cited by 117 publications

References 19 publications

Accumulated hippocampal formaldehyde induces age-dependent memory decline

Accumulated hippocampal formaldehyde induces age-dependent memory decline

Avirulence Protein 3a (AVR3a) from the Potato Pathogen Phytophthora infestans Forms Homodimers through Its Predicted Translocation Region and Does Not Specifically Bind Phospholipids

Formalin-Fixed, Paraffin-Embedded Tissues (FFPE) as a Robust Source for the Profiling of Native and Protease-Generated Protein Amino Termini

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