Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with chronic renal failure are characterized by increased plasma levels of C-reactive protein (CRP) and advanced glycation end products (AGE). AGE have been identified as a class of proinflammator mediators. To investigate whether AGE can stimulate hepatocytes to produce CRP, primary human fetal hepatocytes (HFH) were incubated with AGE-modified human serum albumin (AGE-HSA) or conditioned medium from AGE-HSA-stimulated monocytes (AGE-MCM). CRP concentrations in the supernatants were determined by an ELISA and CRP mRNA levels were determined by a quantitative RT-PCR. Exposure of HFH with AGE-HSA for 12-72 h did not change CRP concentrations in the supernatants. CRP protein and mRNA expression were significantly upregulated in a time- and dose-dependent manner when HFH were incubated with AGE-MCM. This stimulating effect was partially inhibited when AGE-MCM were preincubated with antibodies against interleukin-6 (anti-IL-6), interleukin-1 beta (anti-IL-1 beta), or soluble IL-1 receptor and was completely inhibited when AGE-MCM were preincubated with anti-IL-6 and anti-IL-1 beta simultaneously. The inhibiting effect did not occur when AGE-MCM was preincubated with antibody of tumour necrosis factor-alpha (anti-TNF-alpha) and soluble TNF receptor. Exposure of HFH with exogenous IL-6 and IL-1 beta, at the same concentrations as contained in AGE-MCM, also increased CRP production, but exogenous TNF-alpha had no effect. These results suggest that AGE cannot directly stimulate hepatocytes to produce CRP, but rather indirectly enhance CRP expression via stimulation of IL-6 and IL-1 beta production by human monocytes.
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PMID:Advanced glycation end products upregulate C-reactive protein synthesis by human hepatocytes through stimulation of monocyte IL-6 and IL-1 beta production. 1802 44

Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state.
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PMID:Elimination of endogenous toxin, creatinine from blood plasma depends on albumin conformation: site specific uremic toxicity & impaired drug binding. 2138 72