Dataset Information

Proteome Profiling of Cerebral Vessels in Rhesus Macaques: Dysregulation of Antioxidant Activity and Extracellular Matrix Proteins Contributes to Cerebrovascular Aging in Rhesus Macaques.

ABSTRACT: Aging is a major risk factor for cerebrovascular disease; however, the molecular mechanisms of cerebrovascular aging remain to be clarified. The aim of this study was to reveal the molecular signaling pathways involved in cerebrovascular aging. This study used high-resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in combination with quantitative 6-plex tandem mass tag labeling, to profile protein changes in brain vessels from three groups of healthy rhesus macaques (3-years, 6-years, and 20-years). Western blot analyses were used to validate the proteomic data. A total of 2,934 proteins were identified and analyzed. Twenty-two proteins were continuously downregulated with increasing age, while three proteins were continuously upregulated. When comparing Group C vs. Group B, 270 proteins were downregulated, while 73 proteins were upregulated. All these 368 significantly changed proteins were used for further analysis. Bioinformatic analysis showed that the changed proteins were involved in several signaling pathways during cerebrovascular aging. Proteins in the NRF2 pathway, such as Glutathione S-transferase Mu (GSTM), were consistently downregulated especially after 6-years old, whereas proteins related to miRNA targets in the extracellular matrix (ECM) and membrane receptors were upregulated. Protein-protein interaction networks demonstrated that disorders of energy pathways and serine/threonine kinases were critical during cerebrovascular aging. Data are available via ProteomeXchange under the identifier PXD012306. Our results indicated that during aging, the disorders of energy metabolism and dysfunction of antioxidant activity caused over-production of reactive oxygen species (ROS) may exacerbate cerebrovascular aging. In addition, accumulation of ECM proteins during aging might be closely associated with age-related arterial stiffening and decreased compliance.

SUBMITTER: Wang X

PROVIDER: S-EPMC6819311 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proteome Profiling of Cerebral Vessels in Rhesus Macaques: Dysregulation of Antioxidant Activity and Extracellular Matrix Proteins Contributes to Cerebrovascular Aging in Rhesus Macaques.

Wang Xia X Liu Yifan Y Jia Yangjie Y Liu Haotian H Bao Xinjie X He Zhanlong Z Ge Wei W

Frontiers in aging neuroscience 20191023

Aging is a major risk factor for cerebrovascular disease; however, the molecular mechanisms of cerebrovascular aging remain to be clarified. The aim of this study was to reveal the molecular signaling pathways involved in cerebrovascular aging. This study used high-resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in combination with quantitative 6-plex tandem mass tag labeling, to profile protein changes in brain vessels from three groups of healthy rhesus macaque ...[more]

PMID: 31708766

Similar Datasets

Project description:Breastfeeding is positively associated with several outcomes reflecting early brain development and cognitive functioning. Brain neuroimaging studies have shown that exclusively breastfed children have increased white matter and subcortical gray matter volume compared to formula-fed children. However, it is difficult to disentangle the effects of nutrition in breast milk from other confounding factors that affect brain development, particularly in studies of human subjects. Among the nutrients provided by human breast milk are the carotenoid lutein and the natural form of tocopherol, both of which are selectively deposited in brain. Lutein is the predominant carotenoid in breast milk but not in most infant formulas, whereas infant formulas are supplemented with the synthetic form of tocopherol. In this study, a non-human primate model was used to investigate the effects of breastfeeding versus formula-feeding, as well as lutein and natural RRR-?-tocopherol supplementation of infant formula, on brain maturation under controlled experimental conditions. Infant rhesus macaques (Macaca mulatta) were exclusively breastfed, or were fed infant formulas with different levels and sources of lutein and ?-tocopherol. Of note, the breastfed group were mother-reared whereas the formula-fed infants were nursery-reared. Brain structural and diffusion MR images were collected, and brain T2 was measured, at two, four and six months of age. The mother-reared breastfed group was observed to differ from the formula-fed groups by possessing higher diffusion fractional anisotropy (FA) in the corpus callosum, and lower FA in the cerebral cortex at four and six months of age. Cortical regions exhibiting the largest differences include primary motor, premotor, lateral prefrontal, and inferior temporal cortices. No differences were found between the formula groups. Although this study did not identify a nutritional component of breast milk that could be provided to infant formula to facilitate brain maturation consistent with that observed in breastfed animals, our findings indicate that breastfeeding promoted maturation of the corpus callosum and cerebral cortical gray matter in the absence of several confounding factors that affect studies in human infants. However, differences in rearing experience remain as a potential contributor to brain structural differences between breastfed and formula fed infants.

Project description:Latent viral reservoir is recognized as the major obstacle to achieving a functional cure for HIV infection. We previously reported that arsenic trioxide (As2O3) combined with antiretroviral therapy (ART) can reactivate the viral reservoir and delay viral rebound after ART interruption in chronically simian immunodeficiency virus (SIV)-infected macaques. In this study, we further investigated the effect of As2O3 independent of ART in chronically SIV-infected macaques. We found that As2O3-only treatment significantly increased the CD4/CD8 ratio, improved SIV-specific T cell responses, and reactivated viral latency in chronically SIVmac239-infected macaques. RNA-sequencing analysis revealed that As2O3 treatment downregulated the expression levels of genes related to HIV entry and infection, while the expression levels of genes related to transcription initiation, cell apoptosis, and host restriction factors were significantly upregulated. Importantly, we found that As2O3 treatment specifically induced apoptosis of SIV-infected CD4+ T cells. These findings revealed that As2O3 might not only impact viral latency, but also induce the apoptosis of HIV-infected cells and thus block the secondary infection of bystanders. Moreover, we investigated the therapeutic potential of this regimen in acutely SIVmac239-infected macaques and found that As2O3 + ART treatment effectively restored the CD4+ T cell count, delayed disease progression, and improved survival in acutely SIV-infected macaques. In sum, this work provides new insights to develop As2O3 as a component of the "shock-and-kill" strategy toward HIV functional cure. IMPORTANCE Although antiretroviral therapy (ART) can effectively suppress the viral load of AIDS patients, it cannot functionally cure HIV infection due to the existence of HIV reservoir. Strategies toward HIV functional cure are still highly anticipated to ultimately end the pandemic of AIDS. Herein, we investigated the direct role of As2O3 independent of ART in chronically SIV-infected macaques and explored the underlying mechanisms of the potential of As2O3 in the treatment of HIV/SIV infection. Meanwhile, we investigated the therapeutic effects of ART+As2O3 in acutely SIVmac239-infected macaques. This study showed that As2O3 has the potential to be launched into the "shock-and-kill" strategy to suppress HIV/SIV reservoir due to its latency-reversing and apoptosis-inducing properties.

Dataset Information

Proteome Profiling of Cerebral Vessels in Rhesus Macaques: Dysregulation of Antioxidant Activity and Extracellular Matrix Proteins Contributes to Cerebrovascular Aging in Rhesus Macaques.

Publications

Proteome Profiling of Cerebral Vessels in Rhesus Macaques: Dysregulation of Antioxidant Activity and Extracellular Matrix Proteins Contributes to Cerebrovascular Aging in Rhesus Macaques.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets