High molecular weight aspartic endopeptidase generates a coronaro‐constrictory peptide from the β‐chain of hemoglobin

Barkhudaryan, Nina; Kellermann, Josef; Galoyan, A. A.; Lottspeich, Friedrich

doi:10.1016/0014-5793(93)80224-i

Cited by 51 publications

(29 citation statements)

References 23 publications

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“…Since several hemorphins have been found in rive [3,9] and characterized by their biological properties [13,17], it will be of great interest to find out all the metabolic pathways from hemoglobin to hemorphins. Moreover, Carraway et al suggested the existence of a putative endogenous processing, similar to the renin-angiotensin system, which generates neurotensin-and enkephalin-related peptides in blood circulation [27,28].…”

Section: Resultsmentioning

confidence: 99%

“…It can be noticed that the above-mentioned hemorphins, whatever their source, originated from the same region of the beta-chain of hemoglobin (residues 32-41 of human and 31-40 of bovine hemoglobins) [2,17]. These data suggested that hemoglobin could be a precursor of biologically active peptides, and that hemorphins could be generated in the organism during physiological (catabolism of red cells) or physiopathological (inflammation) hemoglobin proteolysis [2,6,17].…”

Section: Introductionmentioning

confidence: 95%

“…These data suggested that hemoglobin could be a precursor of biologically active peptides, and that hemorphins could be generated in the organism during physiological (catabolism of red cells) or physiopathological (inflammation) hemoglobin proteolysis [2,6,17]. In any case, the actual site of hemorphins generation in the organism is still not elucidated.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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

Dagouassat¹,

Garreau²,

Sannier³

et al. 1996

FEBS Letters

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“…85 The globin fragment has previously been isolated from different brain regions [86][87][88][89] and has been termed LVV-haemorphin-7. Furthermore, the enzymes pepsin, 90 trypsin 88 and a high molecular weight aspartic proteinase present in bovine brain, 91 are capable of cleaving the decapeptide from globin and is suggestive of processing in the central nervous system. Apart from inhibiting opioid activity, 90 our studies indicate that LVV-haemorphin-7 also inhibits neurite outgrowth from E11 chicken sympathetic neurons and stimulates DNA synthesis in neuronal cultures (unpublished observations).…”

Section: Ang IVmentioning

confidence: 99%

Bioactive angiotensin peptides

et al. 1998

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Angiotensin II is recognised as the principle active peptide of the renin-angiotensin system, exerting effects on fluid and electrolyte homeostasis, and cardiovascular control including neural and long term trophic effects. However, recent studies indicate that other angiotensin peptides such as angiotensin III, angiotensin II (1-7) and angiotensin IV, may have specific actions. Interestingly, recent work involving angiotensin IV demonstrates that this peptide binds to specific receptors and may be Keywords: angiotensin metabolites; angiotensin III; angiotensin II(1-7); angiotensin IV; globin Bioactive angiotensin peptidesThe renin-angiotensin system (RAS) was initially identified as a circulating humoral system with the effector peptide, angiotensin II (Ang II), generated by an enzymatic cascade. Angiotensinogen, which is synthesized in the liver, is cleaved by renin, a product of the juxtaglomerular cells of the kidney, to form Ang I, which in turn is cleaved by angiotensinconverting enzyme (ACE) to form Ang II. ACE is membrane bound and predominates on the endothelial cells of all vascular beds. Apart from the production of Ang II in plasma, Ang II, renin and ACE have all been described in tissues such as the brain, kidney, adrenal, vasculature, heart and ovaries. This suggests a separate and distinct RAS in these tissues and implies endocrine, paracrine and autocrine roles for Ang II. Actions of Ang IIAng II regulates blood pressure, fluid volume homeostasis and pituitary hormone release via AT 1 and AT 2 receptors located in the kidney, adrenal gland, and the cardiovascular and nervous systems. [2][3][4][5] In the kidney, for instance, Ang II acts on renal vessels, glomeruli, tubules and renomedullary interstitial cells, to alter renal blood flow, glomerular filtration rate and electrolyte reabsorption.6-9 Ang II also acts on the adrenal cortex to stimulate aldosterone secretion and hence renal sodium reabsorption. 10Ang II is a potent vasoconstrictor, acting directly on vascular smooth muscle and indirectly via facilitation of noradrenaline release from sympathetic terminals. 11,12 In the heart, Ang II exerts positive iono- tropic and chronotropic effects and facilitates sympathetic activity. 13Acting on the brain, Ang II induces fluid and salt ingestion, modulates neuroendocrine systems, including vasopressin and corticotropin releasing factor release, and interacts with the autonomic control of the cardiovascular system to influence blood pressure. 3,14,15 In many instances, these effects are complementary to those of the systemic peptide on peripheral target organs. Thus, systematic Ang II affects the brain through AT 1 receptors located in the circumventricular organs, regions with a deficient blood brain barrier. In addition, endogenous neurally derived Ang II appears to act at many central nervous system sites behind the blood brain barrier. [16][17][18] Most of the classical actions of Ang II are mediated via the AT 1 receptor whereas AT 2 receptor stimulation may cause opposing effects. This was o...

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“…The globin fragment, termed LVVhemorphin-7(LVV-H7), was isolated from sheep brain, using an AT 4 -radioreceptor binding assay and a multistep protein purification procedure. 109 LVV-H7 has also been previously isolated from the brain of other species, [110][111][112][113] reflecting the abundance of the peptide in the central nervous system. Furthermore, the enzymes pepsin, 114 trypsin 112 and a high molecular weight aspartic proteinase present in bovine brain 111 are all capable of processing β-globin to LVV-H7.…”

mentioning

confidence: 99%

Bioactive angiotensin peptides: focus on angiotensin IV

Mustafa

Lee

Chai

et al. 2001

J Renin Angiotensin Aldosterone Syst

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The ability of Ang II (1-7) to mediate and oppose Ang II actions has been recently reviewed. [46][47][48][49] Angiotensin 1-9 and ACE2 Recently, a novel ACE-related enzyme (ACE2) has also been discovered, that catalyses carboxypeptidase cleavage of Ang I to generate Ang (1-9), which subsequently serves as a substrate for the generation of Ang II (1-7). ACE2 is found on the endothelium of coronary and intrarenal vessels and renal tubular epithelium, raising the possibility that the formation of Ang II (1-7) may be important in regulating cardiac and renal function. 50,51 Angiotensin IV Angiotensin IV (Ang IV), originally considered to be biologically inactive, has attracted recent attention because of its ability to elicit many biological actions. Ang IV binds with high affinity to a pharmacologically-distinct binding site, designated the AT 4 receptor. 52,53 This binding site shows highest selectivity for Ang IV, with approximately 10-fold lower affinity for Ang III. Affinities for Ang II and [Sar 1 -Ile 8 ] Ang II are markedly lower, while losartan, PD 123177 and CGP 42112A show no activity. [54][55][56][57][58] The AT 4 -receptor has a distinct distribution pattern in the brain, being found in regions associated with cognitive, sensory and motor function in the guinea pig, 55 sheep 59 and monkey. 60 We recently localised the AT 4 receptor in human forebrain, midbrain, and pons, using an iodinated Ang IV analogue, Norleucine 1 -Ang IV (Nle 1 -Ang IV), a more stable analogue of Ang IV with higher affinity for the AT 4receptor. The distribution of the AT 4 -receptor in the human brain was similar to that reported in other species. 61 The AT 4 -receptor is also found in abundance in peripheral tissues, such as the heart, adrenal cortex, kidney, vascular smooth muscle cells and numerous other tissues. 62 REVIEW Figure 1 Schematic representation of the enzymatic events leading to the formation of angiotensin peptides.

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High molecular weight aspartic endopeptidase generates a coronaro‐constrictory peptide from the β‐chain of hemoglobin

Cited by 51 publications

References 23 publications

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

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

Bioactive angiotensin peptides

Bioactive angiotensin peptides: focus on angiotensin IV

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