ABSTRACT
OBJECTIVE: Dysfunctional metabolisms have contributed towards ischemia-reperfusion (I/R) injury. However, the role of remote ischemic preconditioning (RIP) in I/R injury is not well known. The present study showed alleviated I/R injury in kidneys treated with RIP. MATERIALS AND METHODS: We utilized GC/MS-based metabolomics to characterize the variation of metabolomes. RESULTS: Metabolic category using differential metabolites showed the lower percentage of amino acids in I/R group in comparison to RIP+I/R group, confirming the importance of amino acid metabolism in RIP-treated rat kidney. Further, pathway enrichment analysis showed alanine, aspartate and glutamate metabolism to be involved in the beneficial effects of RIP during renal I/R injury. Furthermore, another crucial enrichment pathway is biosynthesis of unsaturated fatty acids. Other vital metabolites detected in independent component analysis (ICA) analysis were d-glucose, lactic acid and cholesterol. The variation tendency of above-mentioned metabolites was overall consistent with the protective nature of RIP. CONCLUSIONS: These findings elicited a viewpoint that metabolic strategy affected by RIP are linked to underlying mechanisms of RIP and highlighted the importance of metabolic strategy against I/R injury.
Subject(s)
Ischemic Preconditioning/methods , Kidney/physiopathology , Metabolome , Reperfusion Injury , Animals , Female , Gas Chromatography-Mass Spectrometry , Kidney/metabolism , Metabolomics , Rats, Sprague-DawleyABSTRACT
Glycoprotein 96 (gp96), a member of the heat-shock protein family, can elicit priming of antigen-specfic cytotoxic T lymphocytes, when bound to antigenic viral or tumour peptides. We used direct peptide isolation from purified gp96 and microsequencing to show that a virus-specific peptide is bound to gp96 derived from liver tissues of patients with hepatitis B virus (HBV)-induced hepatocellular carcinoma. This virus-specific peptide has potential for engineering tumour vaccines against hepatocellular carcinoma and chronic HBV infection.
Subject(s)
Antigens, Neoplasm/metabolism , Carcinoma, Hepatocellular/metabolism , Heat-Shock Proteins/metabolism , Hepatitis B Core Antigens/metabolism , Hepatitis B/metabolism , Liver Neoplasms/metabolism , Cancer Vaccines , Carcinoma, Hepatocellular/virology , Hepatitis B/complications , Humans , Liver Neoplasms/virology , Peptide Fragments/metabolism , Protein BindingABSTRACT
Many heat shock proteins, e.g. gp96, HSP90, HSP70, etc have elicited rejection and immunotherapy immunogenicity of tumor and infectious diseases. Further study indicated that hsps can chaperone the endogenous repertoire of peptides, and the antigenicity of hsp-peptide complexes lies in the peptides, not HSPs. HSPs present peptides associated with them to MHC class I molecules for recognition by CTL and memory T cells, and elicit cellular immune responses. The latest finding shows that gp96 may present antigenic peptides directly to T lymphocytes functionally as MHC. In recent years the mechanism of immunogenicity and advantages as vaccine therapy of gp96 and HSP70, the two main hsps in mammals have been studied in detail, which offers a new opportunity for immunotherapy of hepatitis B and hepatocellular carcinoma.
