Significant Decrease in Plasma &lt;i&gt;N&lt;/i&gt;-Acetyl-seryl-aspartyl-lysyl-proline Level in Patients with End Stage Renal Disease after Kidney Transplantation

Suzuki, Yosuke; Katagiri, Fumihiko; Sato, Fuminori; Fujioka, Kanako; Sato, Yukie; Fujioka, Takashi; Sato, Yuhki; Mimata, Hiromitsu

doi:10.1248/bpb.b13-00992

Cited by 4 publications

(3 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tetrapeptide AcSDKP is normally present as an endogenous peptide in human plasma and circulating mononuclear cells. It is proteolytically released from its precursor thymosin-β4 by prolyl oligopeptidase (Suzuki et al, 2014 ). AcSDKP evolved anti-fibrotic effects in rats that were either subjected to BDL or treated with CCl 4 , most likely by direct exerting anti-fibrogenic effects on HSC (Chen et al, 2010 ; Zhang et al, 2012a ).…”

Section: Other Compounds With Hepatoprotective Anti-inflammatory or mentioning

confidence: 99%

Hepatoprotective and Anti-fibrotic Agents: It's Time to Take the Next Step

Weiskirchen

2016

Front. Pharmacol.

View full text Add to dashboard Cite

Hepatic fibrosis and cirrhosis cause strong human suffering and necessitate a monetary burden worldwide. Therefore, there is an urgent need for the development of therapies. Pre-clinical animal models are indispensable in the drug discovery and development of new anti-fibrotic compounds and are immensely valuable for understanding and proofing the mode of their proposed action. In fibrosis research, inbreed mice and rats are by far the most used species for testing drug efficacy. During the last decades, several hundred or even a thousand different drugs that reproducibly evolve beneficial effects on liver health in respective disease models were identified. However, there are only a few compounds (e.g., GR-MD-02, GM-CT-01) that were translated from bench to bedside. In contrast, the large number of drugs successfully tested in animal studies is repeatedly tested over and over engender findings with similar or identical outcome. This circumstance undermines the 3R (Replacement, Refinement, Reduction) principle of Russell and Burch that was introduced to minimize the suffering of laboratory animals. This ethical framework, however, represents the basis of the new animal welfare regulations in the member states of the European Union. Consequently, the legal authorities in the different countries are halted to foreclose testing of drugs in animals that were successfully tested before. This review provides a synopsis on anti-fibrotic compounds that were tested in classical rodent models. Their mode of action, potential sources and the observed beneficial effects on liver health are discussed. This review attempts to provide a reference compilation for all those involved in the testing of drugs or in the design of new clinical trials targeting hepatic fibrosis.

show abstract

Section: Other Compounds With Hepatoprotective Anti-inflammatory or mentioning

confidence: 99%

Hepatoprotective and Anti-fibrotic Agents: It's Time to Take the Next Step

Weiskirchen

2016

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Plasma AcSDKP-IS levels showed a gradual decline after kidney transplantation. This was assumed to be due to the acceleration of AcSDKP elimination into the urine with the improvement of kidney function after kidney transplantation [18]. However, plasma AcSDKP-IS level showed a rapid rise on day 70.…”

Section: Journal Of Transplantationmentioning

confidence: 99%

Darbepoetin Alfa Increases Plasma N-acetyl seryl-aspartyl-lysyl-proline Level in Kidney Transplant Recipient: A Case Report

Suzuki¹,

Katagiri²,

Sato³

et al. 2014

J Transplant Technol Res

Self Cite

View full text Add to dashboard Cite

We report a case of elevated plasma N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP)-like immunoreactive substance (IS) level after multiple doses of a recombinant human erythropoietin (rHuEPO), darbepoetin alfa, in a 50 year-old Japanese female who underwent kidney transplantation. Plasma AcSDKP-IS levels showed a gradual decline after kidney transplantation. However, plasma AcSDKP-IS level showed a rapid rise on day 70, and remained at high levels for a period of time and then declined sharply on day 119. After maintaining relatively constant levels from day 119, plasma AcSDKP level showed a rapid rise again on day 168, and declined again on day 238. The two abrupt increases and subsequent sharp decreases of plasma AcSDKP-IS levels correlated temporally with the initiation and discontinuation of the two course of darbepoetin alfa. Although further detailed studies are necessary, administration of darbepoetin alfa may cause a marked increase in plasma AcSDKP level.

show abstract

“…10 In chronic kidney disease, accumulation of AcSDKP has been associated with the exacerbation of anaemia, though AcSDKP levels have been shown to decrease in patients with end-stage renal disease after kidney transplantation. 11 The importance of AcSDKP in anaemic conditions cannot be overemphasised.…”

Section: Introductionmentioning

confidence: 99%

AcSDKP is down-regulated in anaemia induced by <i>Trypanosoma brucei</i> infection in mice

et al. 2017

View full text Add to dashboard Cite

BackgroundAnaemia commonly results from destruction of erythrocytes in the peripheral blood and failure of the bone marrow haematopoietic cells to replenish the erythrocytes. The mechanisms involved in trypanosoma-induced anaemia, including the role of the bone marrow haematopoietic cells are incompletely understood. We studied the responses of a tetrapeptide, AcSDKP, and IL-10, and their association with bone marrow nucleated cells in a Trypanosoma brucei brucei GVR35 experimental infection model.MethodsMouse infection was done intraperitoneally with 1 × 103 trypanosomes/mL. Mice were either infected or left uninfected (N = 100). At days 0, 9, 16, 23, 30, 37, and 44 post-infection, mice were euthanised and blood was collected by cardiac puncture to examine for parasitaemia and packed cell volume (PCV) and then centrifuged for plasma, which was used for cytokine ELISA. The mice's femurs were also dissected and bone marrow was collected for femur cellularity.ResultsPCV dropped from 39.6% to 27% in infected animals by day 9 and remained low (relative to uninfected mice) for the duration of the experiment. AcSDKP levels decreased from day 0 (11.5 × 104 pg/mL) to day 16 (10 × 104), and increased by day 30 (12.6 × 104). There was a significant difference at day 16 (P = 0.023) between the infected and uninfected groups. By contrast, expression of IL-10 markedly increased between day 0 (18.6 pg/mL) and day 16 (145 pg/mL) and decreased by day 30 (42.8 pg/mL). There was also a significant difference in IL-10 expression between infected and uninfected mice at day 16 (P < 0.001). Bone marrow nucleated cells were significantly reduced during periods of low plasma AcSDKP and high plasma IL-10 concentrations (5.4 × 106 infected vs 6.2 × 106 on day 0 and 4.9 × 106 infected vs 10 × 106 uninfected on day 16).ConclusionsThese data unravel a possible negative feedback interaction between AcSDKP and IL-10 in trypanosome infection. More importantly, this study implicates an IL-10/AcSDKP cytokine network in the regulation of bone marrow nucleated cells and provides a new potential mechanism in the pathogenesis of trypanosoma-induced anaemia. Further mechanistic blocking experiments on AcSDKP and IL-10 are recommended to further clarify understanding of the interaction.

show abstract

Significant Decrease in Plasma <i>N</i>-Acetyl-seryl-aspartyl-lysyl-proline Level in Patients with End Stage Renal Disease after Kidney Transplantation

Cited by 4 publications

References 23 publications

Hepatoprotective and Anti-fibrotic Agents: It's Time to Take the Next Step

Hepatoprotective and Anti-fibrotic Agents: It's Time to Take the Next Step

Darbepoetin Alfa Increases Plasma N-acetyl seryl-aspartyl-lysyl-proline Level in Kidney Transplant Recipient: A Case Report

AcSDKP is down-regulated in anaemia induced by <i>Trypanosoma brucei</i> infection in mice

Contact Info

Product

Resources

About