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The ZiBuPiYin recipe regulates proteomic alterations in brain mitochondria-associated ER membranes caused by chronic psychological stress exposure: Implications for cognitive decline in Zucker diabetic fatty rats.

ABSTRACT: Chronic psychological stress (PS) cumulatively affects memory performance through the deleterious effects on hypothalamic-pituitary-adrenal axis regulation. Several functions damaged in cognitive impairment-related diseases are regulated by mitochondria-associated ER membranes (MAMs). To elucidate the role of ZiBuPiYin recipe (ZBPYR) in regulating the MAM proteome to improve PS-induced diabetes-associated cognitive decline (PSD), differentially expressed MAM proteins were identified among Zucker diabetic fatty rats, PSD rats, and PS combined with ZBPYR administration rats via iTRAQ with LC-MS/MS. Proteomic analysis revealed that the expressions of 85 and 33 proteins were altered by PS and ZBPYR treatment, respectively. Among these, 21 proteins were differentially expressed under both PS and ZBPYR treatments, whose functional categories included energy metabolism, lipid and protein metabolism, and synaptic dysfunction. Furthermore, calcium signaling and autophagy-related proteins may play roles in the pathogenesis of PSD and the mechanism of ZBPYR, respectively. Notably, KEGG pathway analysis suggested that 'Alzheimer's disease' and 'oxidative phosphorylation' pathways may be impaired in PSD pathogenesis, while ZBPYR could play a neuroprotective role through regulating the above pathways. Overall, exposure to chronic PS contributes to the evolution of diabetes-associated cognitive decline and ZBPYR might prevent and treat PSD by regulating the MAM proteome.

SUBMITTER: Xu H

PROVIDER: S-EPMC7762487 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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The ZiBuPiYin recipe regulates proteomic alterations in brain mitochondria-associated ER membranes caused by chronic psychological stress exposure: Implications for cognitive decline in Zucker diabetic fatty rats.

Xu Huiying H Zhou Wen W Zhan Libin L Sui Hua H Zhang Lijing L Zhao Chunyan C Lu Xiaoguang X

Aging 20201118 23

Chronic psychological stress (PS) cumulatively affects memory performance through the deleterious effects on hypothalamic-pituitary-adrenal axis regulation. Several functions damaged in cognitive impairment-related diseases are regulated by mitochondria-associated ER membranes (MAMs). To elucidate the role of ZiBuPiYin recipe (ZBPYR) in regulating the MAM proteome to improve PS-induced diabetes-associated cognitive decline (PSD), differentially expressed MAM proteins were identified among Zucker ...[more]

PMID: 33221746

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Project description:Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with multiple etiologies, involving both genetic and environmental factors. With changes associated with modern life, increasing attention has been paid to chronic psychological stressors such as work stress. Chronic psychological stress can induce or aggravate diabetes mellitus, and conversely, with the deterioration of T2DM, patients often experience different degrees of depression, anxiety, and other negative emotions. In order to clarify the role of ZiBuPiYin recipe (ZBPYR) in regulating the liver mitochondria-associated endoplasmic reticulum membrane proteome to improve T2DM with chronic psychological stress, differentially expressed proteins (DEPs) were identified among Zucker lean littermates (control group), chronic psychological stress T2DM rats (model group), and ZBPYR administration rats (ZBPYR group) through iTRAQ with LC-MS/MS. Using Mfuzz soft clustering analysis, DEPs were divided into six different clusters. Clusters 1-6 contained 5, 68, 44, 57, 28, and 32 DEPs, respectively. Given that ZBPYR can alleviate T2DM symptoms and affect exploratory behavior during T2DM with chronic psychological stress, we focused on the clusters with opposite expression trends between model:control and ZBPYR:model groups. We screened out the DEPs in clusters 1, 3, and 4, which may be good candidates for the prevention and treatment of T2DM with chronic psychological stress, and further conducted bioinformatics analyses. DEPs were mainly involved in the insulin signaling pathway, oxidative phosphorylation, tricarboxylic acid cycle, amino acid metabolism, lysosome-related processes, and lipid metabolism. This may indicate the pathogenic basis of T2DM with chronic psychological stress and the potential therapeutic mechanism of ZBPYR. In addition, two key proteins, lysosome-associated protein (Lamp2) and tricarboxylic acid cycle-related protein (Suclg1), may represent novel biomarkers for T2DM with chronic psychological stress and drug targets of ZBPYR. Western blot analyses also showed similar expression patterns of these two proteins in liver MAMs of the model and ZBPYR groups.

Project description:Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with multiple etiologies, involving both genetic and environmental factors. With changes associated with modern life, increasing attention has been paid to chronic psychological stressors such as work stress. Chronic psychological stress can induce or aggravate diabetes mellitus, and conversely, with the deterioration of T2DM, patients often experience different degrees of depression, anxiety, and other negative emotions. To elucidate the role of ZiBuPiYin recipe (ZBPYR) in regulating the liver mitochondria-associated endoplasmic reticulum membrane proteome to improve T2DM with chronic psychological stress, differentially expressed proteins (DEPs) were identified among Zucker lean littermates (control group), chronic psychological stress T2DM rats (model group), and ZBPYR administration rats (ZBPYR group) via iTRAQ with LC-MS/MS. Using Mfuzz soft clustering analysis, DEPs were divided into six different clusters. Clusters 1-6 contained 5, 68, 44, 57, 28, and 32 DEPs, respectively. Given that ZBPYR can alleviate T2DM symptoms and affect exploratory behavior during T2DM with chronic psychological stress, we focused on the clusters with opposite expression trends between model:control and ZBPYR:model groups. We screened out the DEPs in clusters 1, 3, and 4, which may be good candidates for the prevention and treatment of T2DM with chronic psychological stress, and further conducted bioinformatics analyses. DEPs were mainly involved in the insulin signaling pathway, oxidative phosphorylation, tricarboxylic acid cycle, amino acid metabolism, lysosome-related processes, and lipid metabolism. This may indicate the pathogenic basis of T2DM with chronic psychological stress and the potential therapeutic mechanism of ZBPYR. In addition, two key proteins, a lysosome-associated protein (Lamp2) and tricarboxylic acid cycle-related protein (Suclg1), may represent novel biomarkers for T2DM with chronic psychological stress and drug targets of ZBPYR.

Dataset Information

The ZiBuPiYin recipe regulates proteomic alterations in brain mitochondria-associated ER membranes caused by chronic psychological stress exposure: Implications for cognitive decline in Zucker diabetic fatty rats.

Publications

The ZiBuPiYin recipe regulates proteomic alterations in brain mitochondria-associated ER membranes caused by chronic psychological stress exposure: Implications for cognitive decline in Zucker diabetic fatty rats.

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