Concomitant increase in blood plasma levels of immunoreactive hemorphin-7 and β-endorphin following long distance running

Glämsta, Eva‐Lena; Mørkrid, Lars; Lantz, Ingrid; Nyberg, Fred

doi:10.1016/0167-0115(93)90378-l

Cited by 86 publications

(45 citation statements)

References 32 publications

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“…12 They also possess analgesic properties. 13 Serum H7 peptides have been already assayed and found to be decreased in patients with breast cancer 21 and in patients with diabetes. 7 Cathepsin D is a lysosomal enzyme present in macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…These peptides were identified from their amino acid sequence by tandem mass spectrometry as VV-H7 (VVYPWTQRF) and LVV-H7 (LVVYPWTQRF), respectively. 14 These peptides are reported to be mainly generated by digestion of the hemoglobin ␤-chain by cathepsin D. 9 They were isolated from brain, 17 lung, 18 and biological fluids, 13 and they display various biological activities such as angiotensin-converting enzyme inhibition, 19 opioid-like functions, 20 and modulation of inflammation. 12 They also possess analgesic properties.…”

Section: Discussionmentioning

confidence: 99%

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Hemorphin 7 Reflects Hemoglobin Proteolysis in Abdominal Aortic Aneurysm

Dejouvencel

Feron

Rossignol

et al. 2010

ATVB

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Objective-In human abdominal aortic aneurysm, the accumulation of blood-derived cells and proteases within the mural thrombus plays a pivotal role in the evolution toward vessel wall rupture. We sought to identify peptides released from abdominal aortic aneurysm specimens, characterized by an intraluminal thrombus. Methods and Results-Intraluminal thrombus samples were analyzed by differential proteomics, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. A 1309-Da peptide was detected in larger amounts in the newly formed luminal thrombus layer relative to older layers. It was identified as being LVVYPWTQRF (known as LVV-Hemorphin 7), a peptide generated from hemoglobin by cathepsin D. By immunohistochemical analysis, we showed that Hemorphin 7 (H7) colocalizes with cathepsin D and cathepsin G in the luminal layer of the intraluminal thrombus. In vitro, cathepsin G was able to generate H7 peptides at pH 7.4, whereas cathepsin D was only active in acidic conditions. Finally, H7 peptides were shown to be increased 3-to 4-fold in sera of abdominal aortic aneurysm patients relative to controls, and their levels were positively correlated with the volume of the thrombus. Key Words: Human atherothrombosis Ⅲ cathepsin G Ⅲ cathepsin D Ⅲ circulating biomarker Ⅲ thrombus I n human atherothrombosis, the accumulation of bloodderived cells and zymogens contributes to oxidation and proteolysis, together leading to arterial wall destabilization. 1 Depending on the arterial territory, complications associated with atherosclerosis may evolve toward stenosis, frequent in carotid, coronary, and femoral arteries, or outward remodeling, mainly in the aorta. In abdominal aorta, where atherothrombosis frequently develops, evolution toward aneurysm is characterized by the presence of a dynamic intraluminal mural thrombus (ILT), which represents a source of blood-borne proteases participating in extracellular matrix degradation and smooth muscle cell apoptosis, preventing thrombus colonization and cicatrization. 2,3 In the present study, we aimed to look for biomarkers reflecting the pathological remodeling of aortic atherothrombosis associated with the thrombus in abdominal aortic aneurysm (AAA). For this purpose, we used a differential proteomics approach comparing the different layers of human AAA samples, including the thrombus, and the remaining media. We used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), a particularly well-suited technology for detection of peptides and small proteins, including proteolytic fragments. Our hypothesis is that the proteases conveyed by leukocytes (matrix metalloproteases, elastase, cathepsins, etc) or those generated in situ (ie, plasmin, thrombin) may produce protein fragments reflecting the pathological vascular remodeling. 4 Our strategy was thus to compare the profiles of low-molecular-weight proteins and peptides released by AAA samples. Such peptides could be used as biomarkers of the thrombus activity and an...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hemorphin 7 Reflects Hemoglobin Proteolysis in Abdominal Aortic Aneurysm

Dejouvencel

Feron

Rossignol

et al. 2010

ATVB

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“…Fax: (33)46-45-82-47. structure (Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg) was identical to fragment 32--40 of the beta-chain of human hemoglobin. The same authors described the presence of LW-hemorphin-7 in cerebrospinal fluid (CSF) of patients with cerebrovascular bleeding [6], and hemorphin-7 in human plasma after long distance running [7,8]. Many other fragments of the beta-chain of hemoglobin have also been identified in rive [9].…”

Section: Introductionmentioning

confidence: 98%

Generation of VV‐hemorphin‐7 from globin by peritoneal macrophages

Dagouassat¹,

Garreau²,

Sannier³

et al. 1996

FEBS Letters

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Bovine globin has been incubated with mice peritoneal macrophages in order to study its hydrolysis by lysosomal enzymes, among which chiefly cathepsin D. Analysis of resulting peptides, by reversed-phase high-performance liquid chromatography (RP-HPLC), shown the release of a bioaetive peptide, VV-hemorphin-7. When a carboxyl proteinase inhibitor such as pepstatin A was added, no hemorphin was generated. Our results clearly demonstrated that VV-hemorphin-7 generation was principally due to cathepsin D. This study allowed us to hypothetize a possible pathway for in vivo hemorphins appearance from globin catabolism by macrophages.

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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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Concomitant increase in blood plasma levels of immunoreactive hemorphin-7 and β-endorphin following long distance running

Cited by 86 publications

References 32 publications

Hemorphin 7 Reflects Hemoglobin Proteolysis in Abdominal Aortic Aneurysm

Hemorphin 7 Reflects Hemoglobin Proteolysis in Abdominal Aortic Aneurysm

Generation of VV‐hemorphin‐7 from globin by peritoneal macrophages

SwePep, a Database Designed for Endogenous Peptides and Mass Spectrometry

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