Structural Requirements and Mechanism of the Pressor Activity of Leu-Val-Val-hemorphin-7, a Fragment of Hemoglobin β-chain in Rats

Moisan, Steve; Harvey, Nathalie; Beaudry, Guillaume; Forzani, Pascale; Burhop, Kenneth E.; Drapeau, Guy; Rioux, Francis

doi:10.1016/s0196-9781(97)00273-8

Cited by 41 publications

(20 citation statements)

References 22 publications

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“…For example, hemorphins are small peptides generated by enzymatic hydrolysis of hemoglobin or blood (19 -21). Their physiological functions are discussed because they are found in a variety of mammalian tissues and fluids (22)(23)(24)(25)(26)(27). Hemorphin peptides were previously found in brain tissue not proteolytically deactivated (28) but were not detected in tissue that had been proteolytically deactivated (4).…”

Section: Table I Classification and Number Of Peptides In Swepepmentioning

confidence: 99%

SwePep, a Database Designed for Endogenous Peptides and Mass Spectrometry

Fälth

Sköld

Norrman

et al. 2006

Molecular & Cellular Proteomics

125

124

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A new database, SwePep, specifically designed for endogenous peptides, has been constructed to significantly speed up the identification process from complex tissue samples utilizing mass spectrometry. In the identification process the experimental peptide masses are compared with the peptide masses stored in the database both with and without possible post-translational modifications. This intermediate identification step is fast and singles out peptides that are potential endogenous peptides and can later be confirmed with tandem mass spectrometry data. Successful applications of this methodology are presented. The SwePep database is a relational database developed using MySql and Java. The database contains 4180 annotated endogenous peptides from different tissues originating from 394 different species as well as 50 novel peptides from brain tissue identified in our laboratory. Information about the peptides, including mass, isoelectric point, sequence, and precursor protein, is also stored in the database. This new approach holds great potential for removing the bottleneck that occurs during the identification process in the field of peptidomics.

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Section: Table I Classification and Number Of Peptides In Swepepmentioning

confidence: 99%

SwePep, a Database Designed for Endogenous Peptides and Mass Spectrometry

Fälth

Sköld

Norrman

et al. 2006

Molecular & Cellular Proteomics

125

124

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“…Sometimes in vitro stability studies using non-human plasma may give valuable hints for selecting appropriate animal models. Apart from in vivo data from rats [3,16] no related results concerning LVV-H7 are presented in the literature. Therefore, we investigated the metabolism of LVV-H7 in EDTA plasma of the following species: beagle dog, goat, hamster, mouse, rabbit, rat and sheep, and compared the results with human plasma ( Figure 3B).…”

Section: Incubation In Plasma At Different Ph Valuesmentioning

confidence: 99%

“…This is of particular interest since the biological activity of hemorphins is dependent on the peptide length. Enzymatically shortened LVV-H7 molecules possess decreased affinity to the hBRS-3 receptor [5], exhibit decreased inhibitory activity on angiotensinconverting enzyme (ACE) [9,[14][15][16] or change the binding properties to the m-opioid receptor [6]. Therefore, a detailed knowledge of the qualitative and quantitative metabolism characteristics of LVV-H7 is essential.…”

Section: Introductionmentioning

confidence: 99%

Comparative in vitro degradation of the human hemorphin LVV‐H7 in mammalian plasma analysed by capillary zone electrophoresis and mass spectrometry

John¹,

Schulz²,

Forssmann

2007

Biopharm & Drug Disp

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The human hemorphin LVV-H7 (L32VVYPWTQRF41) is a hemoglobin-beta, -gamma, -delta or -epsilon chain derived cationic decapeptide of the micro-opioid receptor binding family. It exhibits potential pharmacological value relevant, for example, for blood pressure regulation, learning performance and Alzheimer's disease. The regulatory potency is strictly dependent on the length of the amino acid sequence which is sensitive towards proteinases from tissues and plasma. To analyse LVV-H7 in vitro degradation in mammalian plasma, a novel multi-component quantitative capillary zone electrophoretic (CZE) procedure was applied, combined with qualitative metabolite profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In all types of plasma, LVV-H7 was N-terminally truncated generating four metabolites (M1-M4) with an intact C-terminus: M1 (V33VYPWTQRF41), M2 (V34YPWTQRF41), M3 (Y35PWTQRF41) and M4 (W37TQRF41). In EDTA plasma these degradation products were detected exclusively, whereas in citrate and heparin plasma four further metabolites appeared resulting from additional C-terminal cleavage of the dipeptide R40F41: M5 (L32VVYPWTQ39), M6 (V33VYPWTQ39), M7 (V34YPWTQ39) and M8 (Y35PWTQ39). In the presence of selective proteinase inhibitors aminopeptidase M and angiotensin-converting enzyme (for N- and C-terminal truncation, respectively) were identified as plasma enzymes responsible for hemorphin degradation. Furthermore, striking inter-mammalian species distinctions were detected revealing strongly differing degradation velocities but similar metabolite patterns.

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“…Functional interactions have been described between hemorphins on the one hand and b-endorphin, growth hormone, prolactin [7], substance P (SP) [18], neuropeptide Y, Met-ENK-Arg-Phe [19] and CRF [17] on the other hand. It has been found out that central CRF and opioid pathways are involved in the interaction between LVVhemorphin-7 and brain serotonergic system [17].…”

Section: Introductionmentioning

confidence: 99%

Hemorphins Act as Homeostatic Agents in Response to Endotoxin-Induced Stress

et al. 2009

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The effect of synthetic LVV-hemorphin-7 and hemorphin-7 on hypothalamo-pituitary-adrenocortical axis activity in response to endotoxin-induced stress was studied. The intraperitoneal (ip) endotoxin (lipopolysaccaride, LPS) (0.5 mg/kg) administration in combination with hemorphin (1 mg/kg) induce significant decrease in plasma corticosterone and modest decrease in plasma levels of tumor necrosis factor-alpha (TNFalpha) in compare with elevated levels of both corticosterone and TNFalpha in plasma of rats received LPS administration alone. Increased activity of calcineurin in both plasma and brain of rats received ip administration of LPS, was recovered under LPS + hemorphin treatment. In two independent proteome analysis, using 2-dimensional fluorescence difference gel electrophoresis and the isotope coded protein label technology, peptidyl-prolyl cis-trans-isomerase A (cyclophilin A) was identified as regulated by hemorphins protein in mouse brain. A therapeutic potential of hemorphins and mechanisms of their homeostatic action in response to endotoxin-induced stress are discussed.

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Structural Requirements and Mechanism of the Pressor Activity of Leu-Val-Val-hemorphin-7, a Fragment of Hemoglobin β-chain in Rats

Cited by 41 publications

References 22 publications

SwePep, a Database Designed for Endogenous Peptides and Mass Spectrometry

SwePep, a Database Designed for Endogenous Peptides and Mass Spectrometry

Comparative in vitro degradation of the human hemorphin LVV‐H7 in mammalian plasma analysed by capillary zone electrophoresis and mass spectrometry

Hemorphins Act as Homeostatic Agents in Response to Endotoxin-Induced Stress

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