Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme

Harmer, Dan W.; Gilbert, Maureen; Borman, Richard A.; Clark, Kenneth L.

doi:10.1016/s0014-5793(02)03640-2

Cited by 799 publications

(731 citation statements)

References 10 publications

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“…ACE2 mRNA displays a wide distribution and is coregionalized with ACE in all tissues. Similar results have been obtained in humans, 10 confirming the hypothesis of a complete local tissue-related RAS. However, ACE2 mRNA expression was different in the organs examined.…”

Section: Discussionsupporting

confidence: 86%

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Angiotensin-Converting Enzyme 2 (ACE2) and ACE Activities Display Tissue-Specific Sensitivity to Undernutrition-Programmed Hypertension in the Adult Rat

et al. 2005

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Abstract-Human epidemiological studies have shown that low birth weight is associated with hypertension in adulthood.Rodent models of intrauterine growth retardation (IUGR) support these findings because offspring from undernourished dams develop hypertension. Angiotensin-converting enzyme 2 (ACE2) is a newly described renin-angiotensin system (RAS) component that competes with ACE for angiotensin peptide hydrolysis and therefore may modulate blood pressure. However, ACE2 potential participation in hypertension programming remains unknown, although RAS alterations were reported in IUGR models. Hence, we first investigated the tissue distribution of ACE2 and ACE in the rat and then whether hypertension programming differentially affects both enzymes. Using multiplex RT-PCR and in situ hybridization, we show that ACE2 mRNA is widely expressed and coregionalized with ACE. Moreover, tissues involved in blood pressure homeostasis (lung, heart, and kidney) express high levels of both enzymes. Enzymatic assays reveal that ACE2 and ACE are coactive in these tissues. Adult (4-month-old) offspring from 70% food-restricted dams throughout gestation (FR30 rats) present mild hypertension, impaired renal morphology, as well as elevated plasma angiotensin II and aldosterone, suggesting alterations of the systemic RAS. In FR30 rats, we show that ACE2 and ACE activities are increased only in the lung, whereas their mRNA expression is not significantly altered, showing that the enzymes display tissue-specific sensitivity to programming. Our results indicate that ACE2 and ACE are coexpressed in numerous rat tissues and that their increased activity in the lung of FR30 rats may participate in hypertension programming.

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Section: Discussionsupporting

confidence: 86%

“…In humans, ACE2 was found at various levels in 72 tissues that also express ACE mRNA. 10 Because ACE2 has also been demonstrated to be a functional receptor for SARS coronavirus, 11 its tissue distribution seems of great importance and appears to be species specific. 12 However, it remains, to our knowledge, not well characterized in the rat.…”

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confidence: 99%

Angiotensin-Converting Enzyme 2 (ACE2) and ACE Activities Display Tissue-Specific Sensitivity to Undernutrition-Programmed Hypertension in the Adult Rat

et al. 2005

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“…17,23 The contribution of the smooth muscle to the Ang II metabolism has not been clarified, although ACE2 transcriptional expression has been demonstrated in human coronary, cerebral, pulmonary, renal, and mesenteric arteries. 24 In the intact adrenal cortical arteries from this study, metabolism of Ang II to Ang (1-7) does not appear to contribute to the vascular relaxations to Ang II. This was evident because the Ang (1-7) receptor antagonist did not alter the relaxations to Ang II.…”

Section: Discussionmentioning

confidence: 49%

Angiotensin II Relaxations of Bovine Adrenal Cortical Arteries

et al. 2008

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Abstract-Angiotensin (Ang) II regulates adrenal steroidogenesis and adrenal cortical arterial tone. Vascular metabolism could decrease Ang II concentrations and produce metabolites with vascular activity. Our goals were to study adrenal artery Ang II metabolism and to characterize metabolite vascular activity. Bovine adrenal cortical arteries were incubated with Ang II (100 nmol/L) for 10 and 30 minutes. Metabolites were analyzed by mass spectrometry. Ang (1-7), Ang III, and Ang IV concentrations were 146Ϯ21, 173Ϯ42 and 58Ϯ11 pg/mg at 10 minutes and 845Ϯ163, 70Ϯ14, and 31Ϯ3 pg/mg at 30 minutes, respectively. Concentration-related relaxations of U46619-preconstricted cortical arteries to Ang II (maximum relaxationϭ29Ϯ3%; EC 50 ϭ3.4 pmol/L) were eliminated by endothelium removal and inhibited by the NO synthase inhibitor, nitro-L-arginine (30 mol/L; maximum relaxationϭ14Ϯ7%). Ang II relaxations were enhanced by the angiotensin type-1 receptor antagonist losartan (1 mol/L; maximum relaxationϭ41Ϯ3%; EC 50 ϭ11 pmol/L). Losartan-enhanced Ang II relaxations were inhibited by nitro-L-arginine (maximum relaxationϭ18Ϯ5%) and the angiotensin type-2 receptor antagonist PD123319 (10 mol/L; maximum relaxationϭ27Ϯ5%). Ang (1-7) and Ang III caused concentration-related relaxations with less potency (EC 50 ϭ43 and 24 nmol/L, respectively) but similar efficacy (maximum relaxationsϭ39Ϯ3% and 48Ϯ5%, respectively) as losartan-enhanced Ang II relaxations. Ang (1-7) relaxations were inhibited by nitro-L-arginine (maximum relaxationϭ16Ϯ4%) and the Ang (1-7) receptor antagonist 7 D -Ala-Ang (1-7) (1 mol/L; maximum relaxationϭ10Ϯ3%) and eliminated by endothelium removal. Thus, Ang II metabolism by adrenal cortical arteries to metabolites with decreased vascular activity represents an inactivation pathway possibly decreasing Ang II presentation to adrenal steroidogenic cells and limits Ang II vascular effects.

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“…Reverse transcription was performed by using SuperScript II (Invitrogen). Specific primers for PCR are described elsewhere (8,(27)(28)(29). Total RNA of HepG2 cells was prepared as recommended by Affymetrix.…”

Section: Methodsmentioning

confidence: 99%

HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor without involving 7SK RNA and positive transcription elongation factor b

Shimizu

Ouchida

Yoshikawa

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The HEXIM1 protein has been shown to form a protein-RNA complex composed of 7SK small nuclear RNA and positive transcription elongation factor b (P-TEFb), which is composed of cyclindependent kinase 9 (CDK9) and cyclin T1, and to inhibit the kinase activity of CDK9, thereby suppressing RNA polymerase II-dependent transcriptional elongation. Here, we biochemically demonstrate that HEXIM1 forms a distinct complex with glucocorticoid receptor (GR) without RNA, CDK9, or cyclin T1. HEXIM1, through its arginine-rich nuclear localization signal, directly associates with the ligand-binding domain of GR. Introduction of HEXIM1 short interfering RNA and adenovirus-mediated exogenous expression of HEXIM1 positively and negatively modulated glucocorticoidresponsive gene activation, respectively. In the nucleus, HEXIM1 was shown to localize in a distinct compartment from that of the p160 coactivator transcriptional intermediary factor 2. Overexpression of HEXIM1 decreased ligand-dependent association between GR and transcriptional intermediary factor 2. Antisense-mediated disruption of 7SK blunted the negative effect of HEXIM1 on arylhydrocarbon receptor-dependent transcription but not on GRmediated one, indicating that a class of transcription factors are direct targets of HEXIM1. These results indicate that HEXIM1 has dual roles in transcriptional regulation: inhibition of transcriptional elongation dependent on 7SK RNA and positive transcription elongation factor b and interference with the sequence-specific transcription factor GR via a direct protein-protein interaction. Moreover, the fact that the central nuclear localization signal of HEXIM1 is essential for both of these actions may argue the crosstalk of these functions.nuclear receptor ͉ RNA-binding protein ͉ ribonucleoprotein ͉ steroid ͉ nuclear localization signal T ranscription is a complex multistep process that relies on highly coordinated actions of a number of cis-and transacting elements (1-3). RNA polymerase II (RNAP II), as the central player in transcription of class II genes, carries out a series of events that include promoter binding, transcription initiation, promoter escape, transcription elongation, and transcription termination. During transcription by RNAP II, phosphorylation of the C-terminal domain of the largest subunit of RNAP II by positive transcription elongation factor b (P-TEFb), which is composed of cyclin-dependent kinase 9 (CDK9) and cyclin T1, is crucial for the transition from the abortive to the productive phase of transcriptional elongation, leading to the generation of full-length RNA transcripts. P-TEFb has been shown to lose its ability to phosphorylate the C-terminal domain when associated with 7SK RNA, a 330-nt small nuclear RNA (4-6).HEXIM1 was first identified as a protein whose expression is induced in vascular smooth muscle cells (VSMC) in response to hexamethylene bisacetamide (HMBA) treatment (7, 8). The HEXIM1 protein consists of 359 amino acids and is tentatively divided into three regions: an N-terminal proline-rich ...

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Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme

Cited by 799 publications

References 10 publications

Angiotensin-Converting Enzyme 2 (ACE2) and ACE Activities Display Tissue-Specific Sensitivity to Undernutrition-Programmed Hypertension in the Adult Rat

Angiotensin-Converting Enzyme 2 (ACE2) and ACE Activities Display Tissue-Specific Sensitivity to Undernutrition-Programmed Hypertension in the Adult Rat

Angiotensin II Relaxations of Bovine Adrenal Cortical Arteries

HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor without involving 7SK RNA and positive transcription elongation factor b

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