Methyl- and acetyltransferases are stable epigenetic markers postmortem

Abstract

Postmortem brain tissue has been reported to be suitable to delineate regional pattern of possible disturbances underlying epigenetic functionality. However, from many parameters that have been detected in postmortem brain regions it is noteworthy that an effect of postmortem interval (PMI), storage time and premortem parameters should not be underestimated. Our previous investigation revealed that tryptophan (TRP) levels in postmortem brain tissue is affected by PMI and storage time. Since, alteration in TRP levels are assumed to be due to protein degradation, we further investigated whether TRP correlates to variables such as RNA, proteins and DNA modulators. In addition, we aimed to elucidate whether established postmortem variables may influence epigenetic parameters. These were investigated in well characterized postmortem human brain tissue originating from the European Brain Bank consortium II (BNEII). We could confirm previous findings, in which some protein levels alter because of prolonged PMI. Similarly, we demonstrated an influence of increased storage period on TRP levels, which might indicate degradation of proteins. Still not all proteins degrade in a similar manner, therefore a specific analysis for the protein of interest would be Camelia Maria Monoranu, Edna Grünblatt, contributed equally and to be considered as equal first authors. Isidro Ferrer, Peter Riederer, to be considered as equal last authors. Camelia Maria Monoranu, Edna Grünblatt, Safa Al-Saraj, Andrea Schmitt, Peter Falkai, Wolfgang Roggendorf, Isidro Ferrer, Peter Riederer-Member of BrainNet Europe II Consortium (BrainNet Europe http://www.brainneteurope.org).Electronic supplementary material The online version of this article (doi:10.1007/s10561-010-9199-z) contains supplementary material, which is available to authorized users. 123Cell Tissue Bank (2011) 12:289-297 DOI 10.1007 recommended. We found that methyltransferase-and acetyltransferase-activities were relatively preserved with PMI and storage duration. In conclusion, preservation of acetyltransferase-and methyltransferaseactivities provides possible evidence of stability for epigenetic studies using postmortem tissue.

Alteration of the pro-oxidant xanthine oxidase (XO) in the thalamus and occipital cortex of patients with schizophrenia

“…The standardized procedure described by Gsell et al (1993) was carried out for the dissection to guaranty the best quality of the tissue used in the study (Monoranu et al 2010). From the fresh brain, the left hemisphere was International Classifi cation of disease: F20.0, paranoid schizophrenia; F20.2, catatonic schizophrenia; F20.5, residual schizophrenia; NK, not known; CPZe, Chlorpromazine equivalent.…”

New insights and updated guidelines for epigenome-wide association studies

“…Although there are some preliminary indications that chromatinmodifying enzymes maintain their activities in postmortem brain (Monoranu et al, 2011), the experience with expression profiling indicates that we need, at a minimum, to be alert to issues like sample acquisition and storage, and for information about tissue pH, agonal factors (Atz et al, 2007), and pharmacological treatments. It should also be noted that even with more accessible organs, procedures that are performed on adults to collect target cells are often less frequently performed on children, a good example being bronchoscopy of the lung and sampling of airway epithelium.…”

Selection of controls in the study of human neurodegenerative diseases in old age

“…In addition, post-mortem delay is accompanied mainly by the progressive deterioration of nucleic acids, proteins, lipids, carbohydrates and metabolites, but some metabolic processes such as histone acetylation and induction of certain transcription factors are still active trying to compensate for the metabolic decay by mimicking in some way the functional responses of penumbra areas associated with infarction (Barrachina et al 2012). Yet, methyl and acetyltransferases are stable epigenetic markers postmortem (Monoranu et al 2011).…”