Establishing the Role of Angiotensin-Converting Enzyme in Renal Function and Blood Pressure Control through the Analysis of Genetically Modified Mice

Bernstein, Kenneth E.; Xiao, Hong; Adams, Jon W.; Frenzel, Kristen; Li, Ping; Shen, Xiao Z.; Cole, Justin M.; Fuchs, Sébastien

doi:10.1681/asn.2004080693

Cited by 10 publications

(6 citation statements)

References 35 publications

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“…Mammalian angiotensin I-converting enzyme (ACE) is a dipeptidyl carboxypeptidase, which plays a key role in the renin-angiotensin system (RAS) by converting angiotensin I into the vasoconstrictor angiotensin II. ACE therefore plays a key role in the regulation of blood homeostasis (Bernstein et al, 2005) and ACE inhibitors are widely prescribed to treat hypertension and other cardiovascular diseases (Hoogwerf, 2010;Slagman et al, 2010). ACE and other components of the RAS have also been shown to be present in adipose tissue where a role in body fat deposition, glucose clearance and energy expenditure has been suggested (de Kloet et al, 2009(de Kloet et al, , 2010Segura and Ruilope, 2007;Jayasooriya et al, 2008;Santos et al, 2008;Weisinger et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Loss of angiotensin-converting enzyme-related (ACER) peptidase disrupts behavioural and metabolic responses to diet in Drosophila melanogaster

Glover

Hodges

Dravecz

et al. 2019

Journal of Experimental Biology

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Drosophila Acer (Angiotensin-converting enzyme-related) encodes a member of the angiotensin-converting enzyme (ACE) family of metallopeptidases that in mammals play roles in the endocrine regulation of blood homeostasis. ACE is also expressed in adipose tissue, where it is thought to play a role in metabolic regulation. Drosophila ACER is expressed in the adult fat body of the head and abdomen and is secreted into the haemolymph. Acer null mutants have previously been found to have reduced night-time sleep and greater sleep fragmentation. ACER may thus be part of a signalling system linking metabolism with sleep. To further understand the role of ACER in response to diet, we measured sleep and other nutrientresponsive phenotypes in Acer null flies under different dietary conditions. We show that loss of Acer disrupts the normal response of sleep to changes in nutrition. Other nutrient-sensitive phenotypes, including survival and glycogen storage, were also altered in the Acer mutant but lipid storage was not. Although the physiological substrate of the ACER peptidase has not been identified, an alteration of the normal nutrient-dependent control of Drosophila insulin-like peptide 5 protein in the Acer mutant suggests insulin/IGF-like signalling as a candidate pathway modulated by ACER in the nutrient-dependent control of sleep, survival and metabolism.

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Section: Introductionmentioning

confidence: 99%

Loss of angiotensin-converting enzyme-related (ACER) peptidase disrupts behavioural and metabolic responses to diet in Drosophila melanogaster

Glover

Hodges

Dravecz

et al. 2019

Journal of Experimental Biology

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“…ACE is a key zinc metalloenzyme of the RAS and is widely distributed in the kidney [17]. The ACE catalyzes the conversion of angiotensin I to the biologically active peptide, angiotensin II, which is involved in the control of fluid electrolyte balance and systemic blood pressure [18].…”

Section: Introductionmentioning

confidence: 99%

Gender Specific Association of RAS Gene Polymorphism with Essential Hypertension: A Case-Control Study

Singh

Jajodia

Kaur

et al. 2014

BioMed Research International

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Renin-angiotensin system (RAS) polymorphisms have been studied as candidate risk factors for hypertension with inconsistent results, possibly due to heterogeneity among various genetic and environmental factors. A case-control association study was conducted to investigate a possible involvement of polymorphisms of three RAS genes: AGT M235T (rs699), ACE I/D (rs4340) and G2350A (rs4343), and AGTR1 A1166C (rs5186) in essential hypertensive patients. A total of 211 cases and 211 controls were recruited for this study. Genotyping was performed using PCR-RFLP method. The genotype and allele distribution of the M235T variant differed significantly in hypertensives and normotensives (OR-CI = 2.62 (1.24–5.76), P = 0.006; OR-CI = 0.699 (0.518–0.943), P = 0.018), respectively. When the samples were segregated based on sex, the 235TT genotype and T allele were predominant in the female patients (OR-CI = 5.68 (1.60-25.10), P = 0.002; OR-CI = 0.522 (0.330–0.826), P = 0.005) as compare to the male patients (OR-CI = 1.54 (1.24–5.76), P = 0.34; OR-CI = 0.874 (0.330–0.826), P = 0.506), respectively. For ACE DD variant, we found overrepresentation of “I”-allele (homozygous II and heterozygous ID) in unaffected males which suggest its protective role in studied population (OR-CI = 0.401 (0.224–0.718); P = 0.0009). The M235T variant of the AGT is significantly associated with female hypertensives and ACE DD variant could be a risk allele for essential hypertension in south India.

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“…It is a dipeptidyl carboxypeptidase and a key player in the renin-angiotensin system (RAS), responsible for the removal of the C-terminal dipeptide of angiotensin I to generate the powerful vasoconstrictor, angiotensin II (for reviews, see Corvol et al, 2004;. ACE is therefore crucially involved in the homeostatic regulation of blood pressure and electrolyte balance and is strongly linked with a number of cardiovascular and renal diseases (Bernstein et al, 2005;Mezzano et al, 2001;Shen et al, 2008b). Indeed, ACE inhibitors that block the formation of angiotensin II are used widely as antihypertensives and to treat congestive heart failure and renal disease (Hoogwerf, 2010;Slagman et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Loss of Angiotensin-converting enzyme-related (ACER) peptidase disrupts night-time sleep in adult Drosophila melanogaster

Çarhan

Tang

Shirras

et al. 2011

Journal of Experimental Biology

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SUMMARYDrosophila Acer (Angiotensin-converting enzyme-related) encodes a member of the angiotensin-converting enzyme family of metallopeptidases that have important roles in the endocrine regulation of blood homeostasis in mammals. Acer is expressed in the embryonic heart of Drosophila and expression in the adult head appears to be regulated by two clock genes. To study the role of Acer in development and in circadian activity, we have generated Acer null mutants by imprecise excision of a P-element and have compared their development and circadian behaviour with that of wild-type flies with the same genetic background. We show that Acer is not required for normal development, but that night sleep, which is clock regulated, is disrupted in adult flies lacking ACER. Acer null adults have reduced night-time sleep and greater sleep fragmentation, but normal levels of daytime sleep. The quality of night sleep in flies fed inhibitors of ACER is affected in a very similar manner. We have shown, using specific antibodies, that ACER is present in the adult fat body of the head and abdomen, and is secreted into the haemolymph. ACER might therefore have a role in cleaving regulatory peptides involved in metabolism and activity behaviour. There are similarities with mammals, where ACE peptidases are also expressed in adipose tissue and are thought to be part of a signalling system linking metabolism with sleep.

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Establishing the Role of Angiotensin-Converting Enzyme in Renal Function and Blood Pressure Control through the Analysis of Genetically Modified Mice

Cited by 10 publications

References 35 publications

Loss of angiotensin-converting enzyme-related (ACER) peptidase disrupts behavioural and metabolic responses to diet in Drosophila melanogaster

Loss of angiotensin-converting enzyme-related (ACER) peptidase disrupts behavioural and metabolic responses to diet in Drosophila melanogaster

Gender Specific Association of RAS Gene Polymorphism with Essential Hypertension: A Case-Control Study

Loss of Angiotensin-converting enzyme-related (ACER) peptidase disrupts night-time sleep in adult Drosophila melanogaster

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