iTRAQ-based quantitative proteomics analysis of Sprague-Dawley rats liver reveals perfluorooctanoic acid-induced lipid metabolism and urea cycle dysfunction

Liu, Hui; Sun, Weizheng; Zhou, Yongbing; Griffin, Nathan; Faulkner, Sam; Wang, Li

doi:10.1016/j.toxlet.2021.12.016

Cited by 20 publications

(4 citation statements)

References 32 publications

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“…STXBP3 has also contributed to the establishment of immunological tolerance in the induction of T cell anergy by the inhibition of the calcineurin-induced calcium influx pathway and inactivation of the nuclear factor of activated T cells (NFAT) (46). GOT2 is ubiquitous in mitochondria and is associated with the regulation of cellular metabolism, especially the malate-aspartate shuttle (47)(48)(49)(50). More importantly, GOT2 was also screened using isobaric tags for relative and absolute quantitation (iTRAQ) proteomics as a functional protein in the lupus mouse model and identified to exhibit a close association with the pathogenesis and development of lupus nephritis by reducing immune inflammation caused by active oxygen.…”

Section: Discussionmentioning

confidence: 99%

STXBP3 and GOT2 predict immunological activity in acute allograft rejection

Yao

Wang

et al. 2022

Front. Immunol.

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BackgroundAcute allograft rejection (AR) following renal transplantation contributes to chronic rejection and allograft dysfunction. The current diagnosis of AR remains dependent on renal allograft biopsy which cannot immediately detect renal allograft injury in the presence of AR. In this study, sensitive biomarkers for AR diagnosis were investigated and developed to protect renal function.MethodsWe analyzed pre- and postoperative data from five databases combined with our own data to identify the key differently expressed genes (DEGs). Furthermore, we performed a bioinformatics analysis to determine the immune characteristics of DEGs. The expression of key DEGs was further confirmed using the real-time quantitative PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemical (IHC) staining in patients with AR. ROC curves analysis was used to estimate the performance of key DEGs in the early diagnosis of AR.ResultsWe identified glutamic-oxaloacetic transaminase 2 (GOT2) and syntaxin binding protein 3 (STXBP3) as key DEGs. The higher expression of STXBP3 and GOT2 in patients with AR was confirmed using RT-qPCR, ELISA, and IHC staining. ROC curve analysis also showed favorable values of STXBP3 and GOT2 for the diagnosis of early stage AR.ConclusionsSTXBP3 and GOT2 could reflect the immunological status of patients with AR and have strong potential for the diagnosis of early-stage AR.

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Section: Discussionmentioning

confidence: 99%

STXBP3 and GOT2 predict immunological activity in acute allograft rejection

Yao

Wang

et al. 2022

Front. Immunol.

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“…Moreover, the results of the western blot and ELISA were normalized by urine creatinine, as described in a previous method that was applied in the investigation of kidney and prostate cancer [ 41 , 42 , 43 ]. There was a possible explanation wherein the previous study found that rats exposed to perfluorooctanoic acid showed body weight loss, significant liver swelling, reduced urea metabolism, a reduced urea concentration in urine, and an increased urea concentration in serum, in comparison with normal control rats [ 53 ]. A high urea content in serum rather than in urine may suggest that perfluorooctanoic acid exposure either decreases the ability of the liver to metabolize urea, or that urea may leak into the bloodstream due to the hepatocyte damage.…”

Section: Discussionmentioning

confidence: 99%

Urine Proteome in Distinguishing Hepatic Steatosis in Patients with Metabolic-Associated Fatty Liver Disease

et al. 2022

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Background: In patients with metabolic-associated fatty liver disease (MAFLD), hepatic steatosis is the first step of diagnosis, and it is a risk predictor that independently predicts insulin resistance, cardiovascular risk, and mortality. Urine biomarkers have the advantage of being less complex, with a lower dynamic range and fewer technical challenges, in comparison to blood biomarkers. Methods: Hepatic steatosis was measured by magnetic resonance imaging (MRI), which measured the proton density fat fraction (MRI-PDFF). Mild hepatic steatosis was defined as MRI-PDFF 5–10% and severe hepatic steatosis was defined as MRI-PDFF > 10%. Results: MAFLD patients with any kidney diseases were excluded. There were 53 proteins identified by mass spectrometry with significantly different expressions among the healthy control, mild steatosis, and severe steatosis patients. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of these significantly changed urinary molecular features correlated with the liver, resulting in the dysregulation of carbohydrate derivative/catabolic/glycosaminoglycan/metabolic processes, insulin-like growth factor receptor levels, inflammatory responses, the PI3K–Akt signaling pathway, and cholesterol metabolism. Urine alpha-1-acid glycoprotein 1 (ORM1) and ceruloplasmin showed the most significant correlation with the clinical parameters of MAFLD status, including liver fat content, fibrosis, ALT, triglycerides, glucose, HOMA-IR, and C-reactive protein. According to ELISA and western blot (30 urine samples, normalized to urine creatinine), ceruloplasmin (ROC 0.78, p = 0.034) and ORM1 (ROC 0.87, p = 0.005) showed moderate diagnostic accuracy in distinguishing mild steatosis from healthy controls. Ceruloplasmin (ROC 0.79, p = 0.028) and ORM1 (ROC 0.81, p = 0.019) also showed moderate diagnostic accuracy in distinguishing severe steatosis from mild steatosis. Conclusions: Ceruloplasmin and ORM1 are potential biomarkers in distinguishing mild and severe steatosis in MAFLD patients.

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“…However, PFOA exposure and how it triggers liver function or hepatic injury is still unclear. A recently conducted experiment on Sprague Dawley rats reported that PFOA significantly changed ALT and induced liver edema and liver toxicity by using mechanisms related to specific protein denaturation [ 30 ]. The mechanism of PFOA’s hepatotoxicity was also studied by using the human liver cell line (HL-7702), and a relationship with specific protein denaturation was reported.…”

Section: Discussionmentioning

confidence: 99%

Human Evidence of Perfluorooctanoic Acid (PFOA) Exposure on Hepatic Disease: A Systematic Review and Meta-Analysis

Choi

Kim

Lee

2022

IJERPH

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Background: Perfluorooctanoic acid (PFOA) is widely used throughout different industries, including the food industry, because it is resistant to heat and prevents water or oil from easily permeating into or contaminating materials coated by PFOA. Although many studies have reported an association between PFOA exposure and the risk of developing hepatic diseases, it is still in debate because they have shown conflicting results. Therefore, this study conducted a systematic review and meta-analysis on the relationship between PFOA exposure and hepatic diseases. Methods: This study searched studies related to hepatic diseases due to PFOA exposure until 31 December 2021, using PubMed, EMBASE, and Web of Science. This study performed a systematic review and meta-analysis through research question development, literature screening, data extraction, and risk of bias evaluation. This study found 8280 studies after excluding duplicate literature and selected 5 studies in the final stage. Among them, two studies were included in the meta-analysis. Results: The results of the meta-analysis showed that the ALT of people exposed to PFOA was 117% higher than the ALT of those not exposed to PFOA, and it was significantly different (OR = 1.167; 95% CI, 1.086–1.254). Conclusion: However, since the number of studies included in the analysis was not large enough to conclude that PFOA exposure was associated with the development of hepatic diseases, more observational studies are needed to confirm its long-term effects.

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iTRAQ-based quantitative proteomics analysis of Sprague-Dawley rats liver reveals perfluorooctanoic acid-induced lipid metabolism and urea cycle dysfunction

Cited by 20 publications

References 32 publications

STXBP3 and GOT2 predict immunological activity in acute allograft rejection

STXBP3 and GOT2 predict immunological activity in acute allograft rejection

Urine Proteome in Distinguishing Hepatic Steatosis in Patients with Metabolic-Associated Fatty Liver Disease

Human Evidence of Perfluorooctanoic Acid (PFOA) Exposure on Hepatic Disease: A Systematic Review and Meta-Analysis

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