Combined Metabonomic and Quantitative Real-Time PCR Analyses Reveal Systems Metabolic Changes in Jurkat T-Cells Treated with HIV-1 Tat Protein

Liao, Wenting; Tan, Guangguo; Zhu, Zhenyu; Chen, Qiuli; Lou, Ziyang; Dong, Xin; Zhang, Wei; Pan, Wei; Chai, Yifeng

doi:10.1021/pr300173c

Cited by 28 publications

(20 citation statements)

References 64 publications

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“…Interestingly, much of the proteomic data has been corroborated by previous publications for on the ETC [10–12] and glycolyic pathway [55–57] albeit in alternative cell types or animal models. Together these data suggest the HIV-1 viral proteins produce chronically dysfunctional mitochondria, and these mitochondrial alterations can contribute to the HAND functional pathology.…”

Section: Discussionmentioning

confidence: 55%

“…Previous work on glycolysis levels in cells exposed to HIV-1 viral proteins have produced varied results. In a variety of cells, exposure to certain HIV-1 viral proteins in vitro or HIV-1 virus in vivo results in increased glycolysis [55–57]. Conversely, isolates of blood from HIV-1 infected individual have also demonstrated decreased glycolysis [58].…”

Section: Discussionmentioning

confidence: 99%

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HIV-1 transgenic rats display mitochondrial abnormalities consistent with abnormal energy generation and distribution

et al. 2016

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With the advent of the combination antiretroviral therapy era (cART), the development of AIDS has been largely limited in the United States. Unfortunately, despite the development of efficacious treatments, HIV-1 associated neurocognitive disorders (HAND) can still develop and as many HIV-1 positive individuals age, the prevalence of HAND is likely to rise because HAND manifests in the brain with very low levels of virus. However, the mechanism producing this viral disorder is still debated. Interestingly, HIV-1 infection exposes neurons to proteins including Tat, Nef, Vpr which can drastically alter mitochondrial properties. Mitochondrial dysfunction has been posited to be a cornerstone of the development of numerous neurodegenerative diseases. Therefore, we investigated mitochondria in an animal model of HAND. Using an HIV-1 transgenic rat model expressing 7 of the 9 HIV-1 viral proteins, mitochondrial functional and proteomic analysis were performed on a subset of mitochondria that are particularly sensitive to cellular changes, the neuronal synaptic mitochondria. Quantitative mass spectroscopic studies followed by statistical analysis revealed extensive proteome alteration in this model paralleling mitochondrial abnormalities identified in HIV-1 animal models and HIV-1 infected humans. Novel mitochondrial protein changes were discovered in the electron transport chain (ETC), the glycolytic pathways, mitochondrial trafficking proteins, and proteins involved in various energy pathways, and these findings correlated well with the function of the mitochondria as assessed by a mitochondrial coupling and flux assay. By targeting these proteins and proteins upstream in the same pathway, we may be able to limit the development of HAND.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

HIV-1 transgenic rats display mitochondrial abnormalities consistent with abnormal energy generation and distribution

et al. 2016

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“…However, five pivotal intermediates of the citrate cycle: citric acid (FC = −0.44), cis-aconitic acid (FC = −0.28), 2-ketoglutaric acid (FC = −1.52), malic acid (FC = −0.38), and fumaric acid (FC = −0.31), were down-regulated in 3D4/2 cells infected with CSFV. This suggested that the citrate cycle might be inhibited by CSFV infection in 3D4/2 cells and this might be caused directly by a reduction of citrate synthesis, which is also found in T-cells treated with HIV-1 Tat protein (Liao et al, 2012). …”

Section: Discussionmentioning

confidence: 89%

“…The decline in malic acid and fumaric acid might be the result of regulation by downstream enzymes of 2-ketoglutaric acid or be attributed to excessive transformation of 2-ketoglutaric acid to proline. Similarly, reverse levels of intermediates in the citrate cycle are also discovered in cells infected by HIV-1 or human cytomegalovirus (HCMV) (Munger et al, 2006; Liao et al, 2012). However, five pivotal intermediates of the citrate cycle: citric acid (FC = −0.44), cis-aconitic acid (FC = −0.28), 2-ketoglutaric acid (FC = −1.52), malic acid (FC = −0.38), and fumaric acid (FC = −0.31), were down-regulated in 3D4/2 cells infected with CSFV.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Profiles in Cell Lines Infected with Classical Swine Fever Virus

et al. 2017

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Viruses require energy and biosynthetic precursors from host cells for replication. An understanding of the metabolic interplay between classical swine fever virus (CSFV) and host cells is important for exploring the complex pathological mechanisms of classical swine fever (CSF). In the current study, and for the first time, we utilized an approach involving gas chromatography coupled with mass spectrometry (GC-MS) to examine the metabolic profiles within PK-15 and 3D4/2 cells infected with CSFV. The differential metabolites of PK-15 cells caused by CSFV infection mainly included the decreased levels of glucose 6-phosphate [fold change (FC) = −1.94)] and glyceraldehyde-3-phosphate (FC = −1.83) during glycolysis, ribulose 5-phosphate (FC = −1.51) in the pentose phosphate pathway, guanosine (FC = −1.24) and inosine (FC = −1.16) during purine biosynthesis, but the increased levels of 2-ketoisovaleric acid (FC = 0.63) during the citrate cycle, and ornithine (FC = 0.56) and proline (FC = 0.62) during arginine and proline metabolism. However, metabolite changes caused by CSFV infection in 3D4/2 cells included the reduced glyceraldehyde-3-phosphate (FC = −0.77) and pyruvic acid (FC = −1.42) during glycolysis, 2-ketoglutaric acid (FC = −1.52) in the citrate cycle, and the elevated cytosine (FC = 2.15) during pyrimidine metabolism. Our data showed that CSFV might rebuild cellular metabolic programs, thus aiding viral replication. These findings may be important in developing targets for new biomarkers for the diagnosis and identification of enzyme inhibitors or metabolites as antiviral drugs, or screening viral gene products as vaccines.

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“…with which metabolic responses to biological interventions or environmental factors are analyzed and modeled (4)(5)(6). Characterizing the metabolome via metabolic profiling provides insight into the state of the organism or substance at a particular moment (7).…”

mentioning

confidence: 99%

Dynamic Metabolic and Transcriptional Profiling of Rhodococcus sp. Strain YYL during the Degradation of Tetrahydrofuran

Yao

Lü

et al. 2014

Appl Environ Microbiol

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cAlthough tetrahydrofuran-degrading Rhodococcus sp. strain YYL possesses tetrahydrofuran (THF) degradation genes similar to those of other tetrahydrofuran-degrading bacteria, a much higher degradation efficiency has been observed in strain YYL. In this study, nuclear magnetic resonance (NMR)-based metabolomics analyses were performed to explore the metabolic profiling response of strain YYL to exposure to THF. Exposure to THF slightly influenced the metabolome of strain YYL when yeast extract was present in the medium. The metabolic profile of strain YYL over time was also investigated using THF as the sole carbon source to identify the metabolites associated with high-efficiency THF degradation. Lactate, alanine, glutarate, glutamate, glutamine, succinate, lysine, trehalose, trimethylamine-N-oxide (TMAO), NAD ؉ , and CTP were significantly altered over time in strain YYL grown in 20 mM THF. Real-time quantitative PCR (RT-qPCR) revealed changes in the transcriptional expression levels of 15 genes involved in THF degradation, suggesting that strain YYL could accumulate several disturbances in osmoregulation (trehalose, glutamate, glutamine, etc.), with reduced glycolysis levels, an accelerated tricarboxylic acid cycle, and enhanced protein synthesis. The findings obtained through 1 H NMR metabolomics analyses and the transcriptional expression of the corresponding genes are complementary for exploring the dynamic metabolic profile in organisms.

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Combined Metabonomic and Quantitative Real-Time PCR Analyses Reveal Systems Metabolic Changes in Jurkat T-Cells Treated with HIV-1 Tat Protein

Cited by 28 publications

References 64 publications

HIV-1 transgenic rats display mitochondrial abnormalities consistent with abnormal energy generation and distribution

HIV-1 transgenic rats display mitochondrial abnormalities consistent with abnormal energy generation and distribution

Metabolic Profiles in Cell Lines Infected with Classical Swine Fever Virus

Dynamic Metabolic and Transcriptional Profiling of Rhodococcus sp. Strain YYL during the Degradation of Tetrahydrofuran

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