Regional differences in protein carboxymethylation in post-mortem human brain.

Author(s): Goggins M, Scott JM, Weir DG

Publication: Clin Sci (Lond), 1998, Vol. 94, Page 677-85

PubMed ID: 9854468 PubMed Review Paper? No

Purpose of Paper

The purpose of this paper was to determine whether protein methylation activity (protein carboxymethylation and N-methylation) is influenced by postmortem interval (PMI), agonal state, and brain region.

Conclusion of Paper

Protein carboxymethylation and N-methylation activities were not altered by a PMI of 12-24 h. Although data was not shown, the authors also report equivalent results among postmortem brain specimens stored at room temperature or at 4 degrees C. Agonal state (slow versus rapid onset of death) did not alter protein methylation activity, although pH that was artificially adjusted in brain specimens did significantly affect protein carboxymethylation and protein N-methylation activities. Differences between brain regions were reported for both protein carboxymethyl group incorporation and N-methyl group incorporation; although results may reflect differences in methylation activity additional confounding variables include differences in methyltransferase activity or the number of unmethylated protein methylation sites. Although data was not shown, the authors report that total protein carboxymethylation activity was not affected by agonal state, and methyl group incorporation was not affected by age or gender.

Studies

Study Purpose

The aims of this study were to determine if protein carboxymethylation and N-methylation activities are affected by PMI or agonal state, and whether the level of methyl group incorporation is specific to the brain region analyzed. A total of 18 autopsy specimens differing in agonal state and PMI were analyzed. Brain specimens collected from different regions were snap frozen in liquid nitrogen and stored at -20 degrees C until analysis.

Summary of Findings:

Protein carboxymethylation and N-methylation activities were not altered by a PMI of 12-24 h. Although data was not shown, the authors also report equivalent results among postmortem brain specimens stored at room temperature or at 4 degrees C. Agonal state did not impact results of a 7 h methylation time course study, although pH that was artificially adjusted in brain specimens did significantly affect protein carboxymethylation and protein N-methylation activities (p<0.05). Differences among brain regions were reported for protein carboxymethyl group incorporation (p<0.01), with the highest levels reported for cortical white matter (p<0.05) and the lowest levels for cerebellum (p<0.05). N-methyl group incorporation also differed between brain regions (p<0.05), with significantly higher levels observed in cortical white matter compared to frontal lobe and basal ganglia (p<0.05). Although data was not shown, the authors report that agonal state did not significantly affect total protein carboxymethylation activity, and gender and age at the onset of death did not significantly affect the level of methyl group incorporation.

Biospecimens

Tissue - Brain

Preservative Types

Frozen

Diagnoses:

Autopsy
Pneumonia/Respiratory Infection
Cardiovascular Disease
Neoplastic - Carcinoma
Normal
Other diagnoses

Platform:

Analyte	Technology Platform
Protein	Radioassay
Protein	Lowry protein assay

Pre-analytical Factors:

Classification	Pre-analytical Factor	Value(s)
Biospecimen Acquisition	Biospecimen location	Frontal cortex Basal ganglia Brain stem Cerebellum Cord Cortical white matter Occipital cortex Parietal cortex Temporal cortex Upper cervical cord
Preaquisition	Postmortem interval	12 h 18 h 24 h
Storage	Storage temperature	Room temperature 4 degrees C
Preaquisition	Rapidity of death	Slow onset death Rapid onset death
Preaquisition	Patient age	21-87 y
Preaquisition	Patient gender	Female Male

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