bims-prodis 2018-07-29 papers

Issue of 2018–07–29
three papers selected by
Nancy Gough, Bioserendipity

J Proteomics. 2018 Jul 18. pii: S1874-3919(18)30289-6. [Epub ahead of print]

Proteomic profiling of human decidual immune proteins during Toxoplasma gondii infection.

Dan Zhang, Xinyue Sun, Liqin Ren, Chunyan Yang, Xianbing Liu, Haixia Zhang, Yuzhu Jiang, Xuemei Hu.

A Toxoplasma gondii infection during pregnancy can result in spontaneous abortion, preterm labor, or congenital fetal defects. The decidual immune system plays a critical role in regulating the immune micro-environment and in the induction of immune tolerance. To better understand the factors that mediate the decidual immune response associated with the T. gondii infection, a large-scale study employing TMT proteomics was conducted to characterize the differential decidual immune proteomes from infected and uninfected human decidual immune cells samples. The decidual immune cells from 105 human voluntary abortion tissues were purified, and of the 5510 unique proteins identified, 181 proteins were found to be differentially abundant (>1.2-fold cutoff, p < 0.05) in the T. gondii-infected decidual immune cells. 11 proteins of 181 differentially expressed proteins associated with trophoblast invasion, placental development, intrauterine fetal growth, and immune tolerance were verified using a quantitative real-time polymerase chain reaction and western blotting. This systematic analysis for the proteomics of decidual immune cells identified a broad range of immune factors in human decidual immune cells, shedding a new insight into the decidual immune molecular mechanism for abnormal pregnancy outcomes associated with T. gondii infection.

Keywords: Decidual immune cells; Proteomics; TMT; Toxoplasma gondii; infection

DOI: https://doi.org/10.1016/j.jprot.2018.07.011

Biochim Biophys Acta. 2018 Jul 18. pii: S0925-4439(18)30260-6. [Epub ahead of print]

Proteomic identification of altered protein O-GlcNAcylation in a triple transgenic mouse model of Alzheimer's disease.

Antonella Tramutola, Nidhi Sharma, Eugenio Barone, Chiara Lanzillotta, Andrea Castellani, Federica Iavarone, Federica Vincenzoni, Massimo Castagnola, D Allan Butterfield, Silvana Gaetani, Tommaso Cassano, Marzia Perluigi, Fabio Di Domenico.

PET scan analysis demonstrated the early reduction of cerebral glucose metabolism in Alzheimer disease (AD) patients that can make neurons vulnerable to damage via the alteration of the hexosamine biosynthetic pathway (HBP). Defective HBP leads to flawed protein O-GlcNAcylation coupled, by a mutual inverse relationship, with increased protein phosphorylation on Ser/Thr residues. Altered O-GlcNAcylation of Tau and APP have been reported in AD and is closely related with pathology onset and progression. In addition, type 2 diabetes patients show an altered O-GlcNAcylation/phosphorylation that might represent a link between metabolic defects and AD progression. Our study aimed to decipher the specific protein targets of altered O-GlcNAcylation in brain of 12-month-old 3×Tg-AD mice compared with age-matched non-Tg mice. Hence, we analysed the global O-GlcNAc levels, the levels and activity of OGT and OGA, the enzymes controlling its cycling and protein specific O-GlcNAc levels using a bi-dimensional electrophoresis (2DE) approach. Our data demonstrate the alteration of OGT and OGA activation coupled with the decrease of total O-GlcNAcylation levels. Data from proteomics analysis led to the identification of several proteins with reduced O-GlcNAcylation levels, which belong to key pathways involved in the progression of AD such as neuronal structure, protein degradation and glucose metabolism. In parallel, we analysed the O-GlcNAcylation/phosphorylation ratio of IRS1 and AKT, whose alterations may contribute to insulin resistance and reduced glucose uptake. Our findings may contribute to better understand the role of altered protein O-GlcNAcylation profile in AD, by possibly identifying novel mechanisms of disease progression related to glucose hypometabolism.

Keywords: Alzheimer disease; Glucose metabolism; Insulin signaling; O-GlcNAcylation; Phosphorylation

DOI: https://doi.org/10.1016/j.bbadis.2018.07.017

Acta Biochim Biophys Sin (Shanghai). 2018 Jul 19.

CC chemokine receptor 7 promotes triple-negative breast cancer growth and metastasis.

Jiao Wu, Lu Li, Jianing Liu, Yang Wang, Zehua Wang, Yangdan Wang, Wenjing Liu, Zhongmei Zhou, Ceshi Chen, Rong Liu, Runxiang Yang.

Metastasis is the leading cause of breast cancer-related death. Chemokine (C-C motif) receptor 7 (CCR7) plays important roles in breast cancer metastasis. However, the role of CCR7 in triple-negative breast cancer (TNBC) has not been fully elucidated. In this study, we found that CCR7 is highly expressed in both TNBC cell lines and breast cancer tissues. CCR7 was knocked down by shRNA in 4T1 and MDA-MB-231, two TNBC cell lines, and we found that the depletion of CCR7 significantly decreased TNBC cell proliferation, migration and invasion in vitro. Furthermore, we confirmed that the knockdown of CCR7 reduced the distant metastasis of 4T1 cells in an orthotopic mouse model. Proteomic analysis in 4T1 cells indicated that several signaling pathways such as epithelial cell adhesion molecule might contribute to CCR7's function in breast cancer metastasis. Our results suggest that CCR7 promotes TNBC metastasis and may serve as a target for breast cancer diagnosis and treatment.

DOI: https://doi.org/10.1093/abbs/gmy077