The inhibitors of hematopoiesis

Guigon, M; Najman, A

doi:10.1002/stem.5530060108

Cited by 16 publications

(9 citation statements)

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“…57 N-Acetyl-Seryl-Aspartyl-Lysyl-Proline N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP or goralatide) is a potent natural inhibitor of hematopoietic stem cell proliferation that is degraded mainly by ACE. 58,59 In vitro, Ac-SDKP is a potent angiogenic factor 60 and inhibits collagen production by cardiac fibroblasts, 61 whereas in vivo, it blocks collagen deposition in the left ventricle of rats with hypertension or myocardial infarction. 62 ACE inhibitor treatment results in a significant increase in plasma Ac-SDKP levels in humans, 63 and in rats, the exogenous application of Ac-SDKP exerts many effects (including inhibition of Ang II-induced cell proliferation, left ventricular macrophage/ mast cell infiltration, and collagen deposition) that are generally associated with ACE inhibitor therapy.…”

Section: Angiotensin 1-7mentioning

confidence: 99%

Signaling by the Angiotensin-Converting Enzyme

Fleming

2006

Circulation Research

161

119

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Abstract-Inhibition of the angiotensin-converting enzyme (ACE) protects against the progression of several cardiovascular diseases. Because of its dual role in regulating angiotensin II and bradykinin levels, the positive clinical effects of ACE inhibitors were thought to be the consequence of concomitant reductions in the production of angiotensin II and the degradation of bradykinin. Recent evidence suggests that some of the beneficial effects of ACE inhibitors on cardiovascular function and homeostasis can be attributed to novel mechanisms. These include the accumulation of the ACE substrate N-acetyl-seryl-aspartyl-lysyl-proline, which blocks collagen deposition in the injured heart, as well as the activation of an ACE signaling cascade that involves the activation of the kinase CK2 and the c-Jun N-terminal kinase in endothelial cells and leads to changes in gene expression. Moreover, at least one other ACE homologue (ACE2) is proposed to counteract the detrimental effects associated with the activation of the classical renin-angiotensin system. These data reveal hitherto unexpected levels of internal regulation of the renin-angiotensin system. (Circ Res. 2006;98:887-896.)

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Section: Angiotensin 1-7mentioning

confidence: 99%

Signaling by the Angiotensin-Converting Enzyme

Fleming

2006

Circulation Research

161

119

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“…2 N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), a negative regulator of hematopoiesis isolated from bone marrow, 3,4 is a natural substrate preferentially hydrolyzed by the N-terminal active site of ACE. 5,6 AcSDKP hydrolysis is blocked by ACE inhibitors (ACEIs) such as captopril and lisinopril in vitro 5,6 and in vivo.…”

mentioning

confidence: 99%

Renal and Metabolic Clearance of N -Acetyl-Seryl-Aspartyl-Lysyl-Proline (AcSDKP) During Angiotensin-Converting Enzyme Inhibition in Humans

et al. 1999

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We investigated the contributions of angiotensin-converting enzyme (ACE) and glomerular filtration to creating the new metabolic balance of the hemoregulatory peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) that occurs during acute and chronic ACE inhibition in healthy subjects. We also studied the effect of chronic renal failure on the plasma concentration of AcSDKP during long-term ACE inhibitor (ACEI) treatment or in its absence. In healthy subjects, a single oral dose of 50 mg captopril (n=32) and a 7-day administration of 50 mg captopril BID (n=10) resulted in a respective 42-fold (range, 18- to 265-fold) and 34-fold (range, 24-fold to 45-fold) increase in the ratio of urinary AcSDKP to creatinine accompanied by a 4-fold (range, 2- to 6.8-fold) and 4.8-fold (range, 2.6- to 11.8-fold) increase in plasma AcSDKP levels. Changes in plasma AcSDKP and in vitro ACE activity over time showed an intermittent reactivation of ACE between each captopril dose. In subjects with chronic renal failure (creatinine clearance<60 mL/min per 1.73 m2), plasma AcSDKP levels were 22 times higher (95% confidence interval, 15 to 33) in the ACEI group (n=35) than the control group (n=23); in subjects with normal renal function, they were only 4.1 times higher (95% confidence interval, 3.2 to 5.3) in the ACEI group (n=19) than the non-ACEI group (n=21). Renal failure itself led to a slight increase in plasma AcSDKP concentration. In conclusion, intermittent reactivation of ACE between doses of an ACEI is the major mechanism accounting for the lack of major AcSDKP accumulation during chronic ACE inhibition in subjects with normal renal function.

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“…On the other hand, inhibitory hematopoiesis of Ac-SDKP is indicated in chronic kidney disease (Guigon and Bonnet, 1995). Thus, it is very important for Ac-SDKP levels to be monitored in chronic kidney disease when treating anemia using ESAs.…”

Section: Clinical Application Of Pre/post-hemodialyzed Subjectsmentioning

confidence: 99%

“…Thymosin β 4 was proposed to be the metabolic precursor of Ac-SDKP by prolyl oligopeptidase (Carvasin et al, 2004). Ac-SDKP is a well-known inhibitor of hematopoietic stem cell proliferation (Guigon and Bonnet, 1995). Moreover, high levels of expression of Ac-SDKP occur in neoplastic diseases such as cancer (Liu et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

On‐line solid‐phase extraction LC‐MS/MS for the determination of Ac‐SDKP peptide in human plasma from hemodialysis patients

Inoue

Ikemura

Tsuruta

et al. 2011

Biomedical Chromatography

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We developed a high-throughput method based on on-line solid-phase extraction liquid chromatography tandem mass spectrometry (SPE-LC-MS/MS) to determine N-terminal thymosin-β fragment peptide (N-acetyl-seryl-aspartyl-lysyl-proline, Ac-SDKP) in human plasma samples. Quantification of Ac-SDKP was performed using direct injection for on-line SPE based on C(18), reversed-phase LC separation and stable isotope dilution electrospray ionization-MS/MS in multiple reaction-monitoring (MRM) mode. The Ac-SDKP-(13)C(6), (15)N(2) (m/z 496 → 137) was synthesized for the internal standard. The MRM ion for Ac-SDKP was m/z 488 → 129 (quantitative ion)/226. The limit of detection and lower limit of quantitation were 0.05 and 0.1 ng/mL in standard solution, respectively. Recovery values were 98.3-100.4% with inter-day (relative standard deviation, RSD, 0.4-14.1%) and intra-day (RSD, 0.8-19.7%) assays. This method was applied to the measurement of Ac-SDKP levels in plasma from hemodialyzed subjects. Concentrations were 0.59 ± 0.23 ng/mL (pre-hemodialyzed subjects, n = 9) and 0.44 ± 0.19 ng/mL (post-hemodialyzed subjects, n = 9). All plasma Ac-SDKP levels were decreased by dialysis. Thus, plasma Ac-SDKP was decreased through dialysis in chronic kidney disease. The findings in this study will be useful for the treatment of anemia in chronic kidney disease with dialysis.

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The inhibitors of hematopoiesis

Cited by 16 publications

References 0 publications

Signaling by the Angiotensin-Converting Enzyme

Signaling by the Angiotensin-Converting Enzyme

Renal and Metabolic Clearance of N -Acetyl-Seryl-Aspartyl-Lysyl-Proline (AcSDKP) During Angiotensin-Converting Enzyme Inhibition in Humans

On‐line solid‐phase extraction LC‐MS/MS for the determination of Ac‐SDKP peptide in human plasma from hemodialysis patients

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