Angiotensin is formed from a precursor, angiotensinogen, which is produced by the liver and found in the a-globulin fraction of plasma. The lowering of blood pressure is a stimulus to secretion of Renin by the kidney into the blood. Renin cleaves from angiotensinogen a terminal decapeptide, Angiotensin I (Ang I). This is further altered by the enzymatic removal of a dipeptide to form Angiotensin II (Ang II). Screening a panel of human-mouse somatic cell hybrids confirmed the assignment of the AGT locus to human chromosome 1. Angiotensin, an octapeptide hormone, is an important physiological effector of blood pressure and volume regulation through vasoconstriction, aldosterone release, sodium uptake and thirst stimulation. It has been shown that mechanical stress causes release of Angiotensin from cardiac myocytes and that Angiotensin acts as an initial mediator of the hypertrophic response. Angiotensin treatment also stimulates phosphorylation of Shc, FAK and MAP kinases and induces MKP-1, indicating stimulation of growth factor pathways. Angiotensin stimulation through AT1 has been shown to activate the JAK/Stat pathway involving a direct interaction between JAK2 and AT1 as demonstrated by co-immunoprecipitation.
Background References
1. Daugherty A et al. Angiotensinogen as a Therapeutic Target for Cardiovascular and Metabolic Diseases. Arterioscler Thromb Vasc Biol. 2024 May
2. Cruz-López EO et al. Angiotensinogen Suppression: A New Tool to Treat Cardiovascular and Renal Disease. Hypertension. 2022 Oct
Sequence Similarity
Belongs to the serpin family.
Tissue Specificity
Expressed by the liver and secreted in plasma.
Post-translational Modification
Beta-decarboxylation of Asp-34 in angiotensin-2, by mononuclear leukocytes produces alanine. The resulting peptide form, angiotensin-A, has the same affinity for the AT1 receptor as angiotensin-2, but a higher affinity for the AT2 receptor.; In response to low blood pressure, the enzyme renin/REN cleaves angiotensinogen to produce angiotensin-1. Angiotensin-1 is a substrate of ACE (angiotensin converting enzyme) that removes a dipeptide to yield the physiologically active peptide angiotensin-2. Angiotensin-1 and angiotensin-2 can be further processed to generate angiotensin-3, angiotensin-4. Angiotensin 1-9 is cleaved from angiotensin-1 by ACE2 and can be further processed by ACE to produce angiotensin 1-7, angiotensin 1-5 and angiotensin 1-4. Angiotensin 1-7 has also been proposed to be cleaved from angiotensin-2 by ACE2 or from angiotensin-1 by MME (neprilysin).; The disulfide bond is labile. Angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized disulfide-bonded form, which preferentially interacts with receptor-bound renin.
Western blot analysis of Angiotensinogen on different lysates with Rabbit anti-Angiotensinogen antibody (ET1612-48) at 1/5,000 dilution.
Lane 1: Hep G2 (Human hepatocellular carcinoma cell) cell lysate Lane 2: Huh7 (Human liver cancer cell) cell lysate Lane 3: HeLa (Human cervical adenocarcinoma cell) cell lysate
Lysates/proteins at 20 µg/Lane. Exposure time: 3 minutes; ECL: K1801
Blocking: 5% NFDM/TBST, 1 hour at room temperature Primary antibody: ET1612-48, 1/5,000 in primary antibody dilution buffer (K1803), overnight at 4 ℃ Secondary antibody: Goat anti-Rabbit IgG-HRP (HA1001), 1/50,000 in 5% NFDM/TBST, 1 hour at room temperature
Predicted band size: 52 kDa Observed band size: 52 kDa
ICC staining Angiotensinogen in Hela cells (green). The nuclear counter stain is DAPI (blue). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS.
ICC staining Angiotensinogen in HepG2 cells (green). The nuclear counter stain is DAPI (blue). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS.
ICC staining Angiotensinogen in LO2 cells (green). The nuclear counter stain is DAPI (blue). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS.
ICC staining Angiotensinogen in 293 cells (green). The nuclear counter stain is DAPI (blue). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS.
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