Tonin–Angiotensin II System in Hypertension

Boucher, R.; García, Raúl; Gutkowska, Jolanta; Demassieux, S.; Genest, Jacques

doi:10.1042/cs055183s

Cited by 7 publications

(7 citation statements)

References 5 publications

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“…Identification of alternate enzymes and Ang I metabolites, though demonstrated in several biological systems, was considered to have no major relevance in terms of biological function or their role in cardiovascular pathology. Although this is not the place for a discussion of these other components, it is worth mentioning the demonstration that tonin could cleave Ang I (Boucher et al, 1977; Cemassieux et al, 1976; Garcia et al, 1976, 1979; Schiffrin et al, 1981), that angiotensin-(1–9) could be produced from Ang I (Campbell et al, 1991, 1995; Donoghue et al, 2000), and that a synthetic tetradecapeptide substrate, angiotensin-(1–14) [Ang-(1–14)], was capable of forming Ang II in vitro (Skeggs, 1993; Skeggs et al, 1958). …”

Section: The Paradigm Shiftmentioning

confidence: 99%

Advances in the Renin Angiotensin System

Ferrario

Ahmad²,

Joyner³

et al. 2010

Advances in Pharmacology

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The contribution of the renin angiotensin system to physiology and pathology is undergoing a rapid reconsideration of its mechanisms from emerging new concepts implicating angiotensin-converting enzyme 2 and angiotensin-(1–7) as new elements negatively influencing the vasoconstrictor, trophic, and pro-inflammatory actions of angiotensin II. This component of the system acts to oppose the vasoconstrictor and proliferative effects on angiotensin II through signaling mechanisms mediated by the mas receptor. In addition, a reduced expression of the vasodepressor axis composed by angiotensin-converting enzyme 2 and angiotensin-(1–7) may contribute to the expression of essential hypertension, the remodeling of heart and renal function associated with this disease, and even the physiology of pregnancy and the development of eclampsia.

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Section: The Paradigm Shiftmentioning

confidence: 99%

Advances in the Renin Angiotensin System

Ferrario

Ahmad²,

Joyner³

et al. 2010

Advances in Pharmacology

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“…Over the years, a number of renin-like enzymes have been reported to release Ang I from either the angiotensinogen molecule or the model substrate tetradecapeptide [Ang- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)]. Cathepsin D and G, acid and neutral proteases, tonin, the serine protease esterase B, a kallikrein-like serine protease, and mouse ␥-nerve growth factor (␥-NGF) are among the enzymes identified as Ang I-forming enzymes (16,17,23,42,56,58,59,73,117,157). Tonin, an enzyme discovered by Boucher et al (17) and present at its highest concentration in the submaxillary gland, forms Ang II directly from the tetradecapeptide substrate [Ang- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)] and from Ang I (117).…”

mentioning

confidence: 99%

“…Cathepsin D and G, acid and neutral proteases, tonin, the serine protease esterase B, a kallikrein-like serine protease, and mouse ␥-nerve growth factor (␥-NGF) are among the enzymes identified as Ang I-forming enzymes (16,17,23,42,56,58,59,73,117,157). Tonin, an enzyme discovered by Boucher et al (17) and present at its highest concentration in the submaxillary gland, forms Ang II directly from the tetradecapeptide substrate [Ang- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)] and from Ang I (117). A neutral protease with Ang I-forming activity that was readily separated from acid proteases and both plasma and renal renin was reported by Husain et al (65,66) in the canine brain.…”

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confidence: 99%

Intracrine angiotensin II functions originate from noncanonical pathways in the human heart

Ferrario

Ahmad

Varagić

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Although it is well-known that excess renin angiotensin system (RAS) activity contributes to the pathophysiology of cardiac and vascular disease, tissue-based expression of RAS genes has given rise to the possibility that intracellularly produced angiotensin II (Ang II) may be a critical contributor to disease processes. An extended form of angiotensin I (Ang I), the dodecapeptide angiotensin-(1-12) [Ang-(1-12)], that generates Ang II directly from chymase, particularly in the human heart, reinforces the possibility that an alternative noncanonical renin independent pathway for Ang II formation may be important in explaining the mechanisms by which the hormone contributes to adverse cardiac and vascular remodeling. This review summarizes the work that has been done in evaluating the functional significance of Ang-(1-12) and how this substrate generated from angiotensinogen by a yet to be identified enzyme enhances knowledge about Ang II pathological actions.

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“…Enzyme II is not identical to tonin, because tonin produces angiotensin II, rather than angiotensin I, has maximal enzymatic activity at pH 6.8 rather than at pH 4.7, and is not inhibited by pepstatin. 29 Cathepsin G differs from enzyme II, since cathepsin G generates angiotensin II and not angiotensin I, 30 has its maximum enzymatic activity at pH 7.5, 19 and is inhibited by diisopropyl fluorophosphate, 19 while enzyme II was not inhibited by 1 x 10" 3 M diisopropyl fluorophosphate.…”

Section: Nonidentity Of Enzyme II With Pepsin Cathepsin D Plasmin mentioning

confidence: 99%

Angiotensin-producing serum enzyme II. Formation by inhibitor removal and proenzyme activation.

Haas¹,

Lewis²,

Scipione³

et al. 1985

Hypertension

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SUMMARY A highly active angiotensin-producing enzyme (enzyme II) was obtained from dog serum by acid treatment and fractionation to remove angiotensinase and converting enzyme, separate an inhibitor, and convert an inactive precursor (proenzyme II) to enzyme II. Proenzyme II was found to be converted to enzyme II by an endogenous activating enzyme identified as plasmin. Conversion was also caused by the interaction of bacterial streptokinase with human proactivator, by trypsin, and by an activator formed from liver tissue extract and dog serum. Neither plasma kallikrein nor the labile, human extrinsic tissue-type plasminogen activator induced activation. The inhibitor, which normally blocks the activation of proenzyme II, was unusually stable against high temperatures and extremes of pH, and it was not identical to any of the six known protease inhibitors of serum. Enzyme II was not identical to other angiotensin-producing enzymes such as enzyme I, renin, cathepsin D, pepsin, ptasmin, tonin, or cathepsin G. Enzyme II reacted maximally at pH 4.7 and produced up to 2250 ng of angiotensin I/ml serum/hr from the substrate of dog serum (i.e., amounts 3200-fold higher than that produced by endogenous renin of normal dog serum). Since at pH 7.2, angiotensin I formation is still about 30 times higher than that of renin, enzyme II may be physiologically active under some conditions. (Hypertension 7: 938-947, 1985) KEY WORDS • angiotensin I • serum • plasminogen • plasmin * prorenin renin • kallikrein • activators • inhibitors • substrate I N the past few years we have observed two highly active angiotensin-producing enzymes different from renin: enzyme I, present in the serum of dogs, guinea pigs, rabbits, and rats after immunization with renin from the kidneys of hogs, cattle, dogs, rabbits, and humans, 1 and enzyme II, obtained from the serum of normal dogs and in a higher concentration from the serum of nephrectomized dogs. 2^1Enzyme II is normally present in serum as an inactive precursor referred to as proenzyme II and is accompanied by its substrate, by an endogenous activating enzyme, and by an inhibitor of the activating enzyme. The purpose of the present study was not only to clarify the mechanisms involved in the activation

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Tonin–Angiotensin II System in Hypertension

Cited by 7 publications

References 5 publications

Advances in the Renin Angiotensin System

Advances in the Renin Angiotensin System

Intracrine angiotensin II functions originate from noncanonical pathways in the human heart

Angiotensin-producing serum enzyme II. Formation by inhibitor removal and proenzyme activation.

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