Dataset Information

Proteomic analysis of mitochondria isolated from the frontal cortex and hippocampus of apolipoprotein E knockout mice treated with Alda-1, an activator of mitochondrial aldehyde dehydrogenase (ALDH2)

ABSTRACT: Recently, it has been shown that mitochondrial dysfunction and oxidative stress play important roles in the pathogenesis of neurodegeneration. Mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme responsible for the detoxification of reactive aldehydes – the end products of lipid peroxidation, is considered to exert protective function in mitochondria. The aim of our study was to use the methods of differential proteomics in concert with molecular and morphological techniques to elucidate the changes in the frontal cortex and hippocampus of apolipoprotein E knockout (apoE-/-) mice (an animal model of the early stages of Alzheimer’s disease) upon treatment with Alda-1 – a small molecular weight activator of ALDH2.

INSTRUMENT(S): LTQ

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Aneta Stachowicz

LAB HEAD: Rafał Olszanecki

PROVIDER: PXD004022 | Pride | 2017-02-23

REPOSITORIES: Pride

ACCESS DATA

Publications

Proteomic Analysis of Mitochondria-Enriched Fraction Isolated from the Frontal Cortex and Hippocampus of Apolipoprotein E Knockout Mice Treated with Alda-1, an Activator of Mitochondrial Aldehyde Dehydrogenase (ALDH2).

Stachowicz Aneta A Olszanecki Rafał R Suski Maciej M Głombik Katarzyna K Basta-Kaim Agnieszka A Adamek Dariusz D Korbut Ryszard R

International journal of molecular sciences 20170217 2

The role of different genotypes of apolipoprotein E (apoE) in the etiology of Alzheimer's disease is widely recognized. It has been shown that altered functioning of apoE may promote 4-hydroxynonenal modification of mitochondrial proteins, which may result in mitochondrial dysfunction, aggravation of oxidative stress, and neurodegeneration. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme considered to perform protective function in mitochondria by the detoxification of the end products ...[more]

PMID: 28218653

Similar Datasets

Project description:Cryo-thermal therapy has been proven to be a promising novel systemic strategy for advanced breast cancer, resulting in higher incidence of tumor regression and enhanced remission of metastasis. The mechanism by which such strategy boosts the anti-tumor activity remains unclear. To gain a system-wide understanding of the anti-tumor response, here we utilized a spontaneous metastatic mouse model and quantitative proteomics to compare the N-glycoproteome changes following treatment or not in 94 serum samples over 8 time points. We quantified 231 high confident N-glycosylated serum proteins in total using iTRAQ labeling shotgun proteomic. 53 of them showed significant regulatory patterns over time course, in which we identified acute phase response as the most enhanced pathway and markedly distinguished in the hierarchical proteome profile. We therefore investigated the function of acute response in tumoricidal effect using quantitative parallel reaction monitoring proteomics and flow cytometry upon 23 out of 53 significant proteins. We found that cryo-thermal therapy reshaped the tumor chronic inflammatory microenvironment to an ‘acute’ phenotype, accompanying ‘acute’ and markedly high expression of acute phase proteins and their key upstream regulator -interleukin 6. Such IL-6 mediated ‘acute’ phenotype drove the tumor site from a Th2 immunosuppressive, pro-tumorigenic to a Th1 immunostimulatory, tumouricidal phenotype, inducing a switch from IL-4 and Treg-promoting ICOSL expression to Th1-promoting IFN –γand IL-12 production, skewing to complement system activation and CD86+MHCII+ dendritic cells maturation, and enhancing the proliferation of Th1 memory cells. We also found an increased production of tumor metastatic inhibitors under such ‘acute’ environment, favoring the anti-metastatic effect. In this study, we revealed that IL-6 mediated ‘acute’ inflammatory profile played a key role to suppress immunosuppression and wake up the anti-tumor activity, recovering host metabolism and physiology. This could guide us a better understanding to improve this cancer treatment for better therapeutic effect.

Dataset Information

Proteomic analysis of mitochondria isolated from the frontal cortex and hippocampus of apolipoprotein E knockout mice treated with Alda-1, an activator of mitochondrial aldehyde dehydrogenase (ALDH2)

Publications

Proteomic Analysis of Mitochondria-Enriched Fraction Isolated from the Frontal Cortex and Hippocampus of Apolipoprotein E Knockout Mice Treated with Alda-1, an Activator of Mitochondrial Aldehyde Dehydrogenase (ALDH2).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure