Biology subjects

McClatchy, D. B.

Publications and source records attributed to McClatchy, D. B..

3 recordsLinked to original sources

bioRxiv2018

Quantitative Temporal Analysis of Protein Dynamics in Maladaptive Cardiac Remodeling

Maladaptive cardiac remodeling (MCR) is a complex dynamic process common to many heart diseases. MCR is characterized as a temporal progression of global adaptive and maladaptive perturbations. The complex nature of this process clouds a comprehensive understanding of MCR, but greater insight into the processes and mechanisms has the potential to identify new therapeutic targets. To provide a deeper understanding of this important cardiac process, we applied a new proteomic technique, PALM (Pulse Azidohomoalanine in Mammals), to quantitate the newly-synthesized protein (NSP) changes during the progression of isoproterenol (ISO)-induced MCR in the mouse left ventricle. This analysis revealed a complex combination of adaptive and maladaptive alterations at acute and prolonged time points including the identification of proteins not previously associated with MCR. We also combined the PALM dataset with our published protein turnover rate dataset to identify putative biochemical mechanisms underlying MCR. The novel integration of analyzing NSPs together with their protein turnover rates demonstrated that alterations in specific biological pathways (e.g., inflammation and oxidative stress) are produced by differential regulation of protein synthesis and degradation.

pathology↗

bioRxiv2017

Amyloid accumulation drives proteome-wide alterations in mouse models of Alzheimers disease like pathology

Amyloid beta (A{beta}) peptides impair multiple cellular pathways in the brain and play a causative role in Alzheimers disease (AD) pathology, but how the brain proteome is remodeled during this process is unknown. To identify new protein networks associated with AD-like pathology, we performed global quantitative proteomic analysis in three mouse models at pre- and post-symptomatic ages. Our analysis revealed a robust and consistent increase in Apolipoprotein E (ApoE) levels in nearly all transgenic brain regions with increased A{beta} levels. Taken together with prior findings on ApoE driving A{beta} accumulation, this analysis points to a pathological dysregulation of the ApoE-A{beta} axis. We also found dysregulation of protein networks involved in excitatory synaptic transmission consistent with AD pathophysiology. Targeted analysis of the AMPA receptor complex revealed a specific loss of TARP{gamma}-2, a key AMPA receptor trafficking protein. Expression of TARP{gamma}-2 in vivo in hAPP transgenic mice led to a restoration of AMPA currents. This database of proteome alterations represents a unique resource for the identification of protein alterations responsible for AD.\n\nHighlightsO_LIProteomic analysis of mouse brains with AD-like pathology reveals stark remodeling\nC_LIO_LIProteomic evidence points to a dysregulation of ApoE levels associated with A{beta} clearance rather than production\nC_LIO_LICo-expression analysis found distinctly impaired synapse and mitochondria modules\nC_LIO_LIIn-depth analyses of AMPAR complex points to loss of TARP{gamma}-2, which may compromise synapses in AD\nC_LI\n\neTOC BlurbProteome-wide profiling of brain tissue from three mouse models of AD-like pathology reveals A{beta}, brain region, and age dependent alterations of protein levels. This resource provides a new global protein expression atlas for the Alzheimers disease research community.

neuroscience↗

bioRxiv2016

HILAQ: A Novel Strategy for Newly Synthesized Protein Quantification

Here we describe a new strategy, HILAQ (Heavy Isotope Labeled Azidohomoalanine Quantification), to rapidly quantify the molecular vulnerability profile to oxytosis. HILAQ quantified more than 1,900 Newly Synthesized Proteins (NSP) after 1h pulse labeling in HEK293T cell line. Compared with the previous published QuaNCAT protocol, the HILAQ strategy simplifies newly synthesized proteome analysis and achieves higher sensitivity.

biochemistry↗