Disease relevance of Ace

• We show that mice deficient for Ace show markedly improved disease, and also that recombinant ACE2 can protect mice from severe acute lung injury [1].
• The importance of ACE in these cell types was revealed by generating Ace -/- mice, which exhibit multiple abnormalities including renal structural defects and functions, hypotension, and male sterility [2].
• Using a mouse model of atherosclerosis induced by heterozygosity for apolipoprotein E gene disruption and an atherogenic diet, we have studied the impact on atherogenesis of a mutation that changes the level of function of Ace [3].
• Here, we demonstrate that mice infected with trypomastigotes develop potent edema after treatment with the angiotensin-converting enzyme (ACE) (or kininase II) inhibitor captopril [4].
• The HSV-1 mutant in1814, which contains a 12-bp insertion that compromises the transcriptional function of VP16, replicated to a low level if at all in the trigeminal ganglia of mice (I. Steiner, J. G. Spivack, S. L. Deshmane, C. I. Ace, C. M. Preston, and N. W. Fraser (1990). J. Virol. 64, 1630-1638; Valyi-Nagy et al., unpublished data) [5].

High impact information on Ace

• Here we investigate the role of the Ace gene in blood pressure control and reproduction using mice generated to carry an insertional mutation that is designed to inactivate both forms of ACE [6].
• Epitopes associated with the MHC restriction site of T cells. II. Somatic generation of Iat epitopes on T cells in radiation bone marrow chimeras [7].
• Role of human chromosome 11 in determining surface antigenic phenotype of normal and malignant cells. Somatic cell genetic analysis of eight antigens, including putative human Thy-1 [8].
• Regulation of macrophage function by interferon-gamma. Somatic cell genetic approaches in murine macrophage cell lines to mechanisms of growth inhibition, the oxidative burst, and expression of the chronic granulomatous disease gene [9].
• A series of stable cell mutants of mouse fibroblasts were previously isolated (Roos, D. S. and R. L. Davidson, 1980, Somatic Cell Genet., 6:381-390) that exhibit varying degrees of resistance to the fusion-inducing effect of polyethylene glycol (PEG), but are morphologically similar to the parental cells from which they were derived [10].

Biological context of Ace

• This phenotype is virtually identical to that seen in angiotensinogen-deficient (Agt-/-) and angiotensin-converting enzyme-deficient (Ace -/-) mice that are unable to synthesize angiotensin II [11].
• LVMI under normotension was the same regardless of the Ace genotype, but the slopes of the LVMI/SBP curves increased in the three- vs. one-copy group by approximately 50% upon 3- or 6-wk PO [12].
• RESULTS: The normal postnatal up-regulation of kininase II was organ-specifically suppressed in Agtr1-/- kidneys at 2 and 3 weeks of age [13].
• The blood pressures of the mice having from one to three copies of the Ace gene did not differ significantly, but the heart rates, heart weights, and renal tubulointerstitial volumes decreased significantly with increasing Ace gene copy number [14].
• Surprisingly, quantitative changes in Ace gene expression over a threefold range do not affect blood pressures [15].

Anatomical context of Ace

• The angiotensin-converting enzyme (ACE; EC 3.4.15.1) gene (Ace) encodes both a somatic isozyme found in blood and several other tissues, including the epididymis, and a testis-specific isozyme (testis ACE) found only in developing spermatids and mature sperm [16].
• Cultured fibroblasts without TACE activity, when transfected with cDNA encoding for the testicular isozyme of ACE (ACET), synthesized and secreted ACET normally after a proteolytic cleavage near the C terminus [17].
• This diminished amount of ADAM3 in the Triton X-114 detergent-enriched phase may explain the inability of Clgn(-/-) and Ace(-/-) sperm to bind to the zona pellucida [18].
• Male mice deficient for the calmegin (Clgn) or the angiotensin-converting enzyme (Ace) gene show impaired sperm migration into the oviduct and loss of sperm-zona pellucida binding ability in vitro [18].
• The unique molecular mass, N-terminal sequence and activity on CHO cells indicate that this factor is not zonula occludens toxin (Zot) or accessory cholera enterotoxin (Ace) or the Hly A haemolysin [19].

Associations of Ace with chemical compounds

• We have previously shown that sperm-specific expression of transgenic germinal ACE in Ace -/- male mice restores fertility without curing their other abnormalities (Ramaraj, P., Kessler, S. P., Colmenares, C. & Sen, G. C. (1998) J. Clin. Invest. 102, 371-378) [20].
• We conclude that (1) ACE is essential for the maintenance of normal blood pressure; (2) subnormal levels of ACE affect the blood pressure responses to infused angiotensin I and bradykinin in vivo; and (3) compensations for inactivation of one Ace copy, which include increased expression of renin, normalize blood pressure in heterozygotes [21].
• 5. Although injection of kininase II inhibitor, lisinopril together with sodium deoxycholic acid did not alter the scratching behaviour, phosphoramidon, a neutral endopeptidase inhibitor, significantly increased the frequency of scratching [22].
• The latency in B/N-Kitasato rat was prolonged by administration of a bradykinin (BK) B2 receptor antagonist, FR173657 (30 mg/kg, p.o.), whereas it was shortened by pretreatment with a kininase II inhibitor, captopril (10 mg/kg, i.p.). Both agents did not affect the latency in B/N-Katholiek rats [23].
• In the Ace(-/-) mice, while ADAM2 was found normally in the sperm, ADAM3 disappeared from the Triton X-114 detergent-enriched phase after phase separation, which suggests that ACE is involved in distributing ADAM3 to a location where it can participate in sperm-zona pellucida binding [18].

Other interactions of Ace

• This marker maps near Ace, Gh, and Ngfr positional candidate genes [24].
• Expression of p53 protein in the UV/VEA group was maximum at 12 h after UV exposure, whereas in the Ace/UV- and VEA/UV-treated mice, maximum p53 immunostaining was statistically higher at 15 h (P = 0.03) [25].
• The telomerase activity of carcinomas from the UV/VEA-treated mice was statistically lower than that of the Ace/UV-treated mice (P = 0.05) [25].

Analytical, diagnostic and therapeutic context of Ace

• We have used gene targeting to vary the amounts of angiotensinogen and angiotensin-converting enzyme (ACE) synthesized from their genes (Agt and Ace) [15].
• We evaluated whether an oral administration of Chl (2.0, 6.0 and 10.0 mg/kg), given 1 h before an i.p. administration of Ace (100 mg/kg), could modulate the SCEs produced by the mutagen [26].
• The first aim of the present study was to determine the capacity of Ace to increase the rate of sister-chromatid exchanges (SCEs) in mouse bone marrow cells in vivo, as well as to determine its capacity to modify the mitotic index (MI) and the average generation time (AGT) [26].
• We tested four doses of Ace (from 0.4 to 400.0 mg/kg), including a negative and a positive control group (distilled water and cyclophosphamide, respectively) [27].

References