Regulated Expression of Testis Angiotensin-Converting Enzyme during Spermatogenesis in Mice1

Langford, Kimberly G.; Zhou, Yifeng; Russell, Lonnie D.; Wilcox, Josiah N.; Bernstein, Kenneth E.

doi:10.1095/biolreprod48.6.1210

Cited by 87 publications

(88 citation statements)

References 21 publications

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“…This cDNA fragment was generated by PCR from cloned ACE cDNA with the primers 5 Ј -CAGAACGCGTGCAGACCTA-GAGACTGATGAAGC-3 Ј and 5 Ј -CAGACGATATCGACCTT-TAATTGTATTCACAG-3 Ј . The fragment incorporates 2.2 kb of ACE cDNA sequence including all of the somatic ACE coding exons (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) downstream of the neomycin cassette in the previous construct and 216 bp of 3 Ј untranslated region including a poly-adenylation site. The cDNA fragment contains a consensus 3 Ј splice acceptor sequence (GCAG) immediately 5 Ј of the coding region.…”

Section: Creation Of Mice With a Mutant Ace Allelementioning

confidence: 99%

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The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice.

Esther¹,

Marino²,

Howard³

et al. 1997

J. Clin. Invest.

266

211

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Angiotensin-converting enzyme (ACE) generates the vasoconstrictor angiotensin II, which plays a critical role in maintenance of blood pressure in mammals. Although significant ACE activity is found in plasma, the majority of the enzyme is bound to tissues such as the vascular endothelium. We used targeted homologous recombination to create mice expressing a form of ACE that lacks the COOH-terminal half of the molecule. This modified ACE protein is catalytically active but entirely secreted from cells. Mice that express only this modified ACE have significant plasma ACE activity but no tissue-bound enzyme. These animals have low blood pressure, renal vascular thickening, and a urine concentrating defect. The phenotype is very similar to that of completely ACE-deficient mice previously reported, except that the renal pathology is less severe. These studies strongly support the concept that the tissue-bound ACE is essential to the control of blood pressure and the structure and function of the kidney. ( J. Clin. Invest. 1997. 99:2375-2385.)

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Section: Creation Of Mice With a Mutant Ace Allelementioning

confidence: 99%

“…20 mg of protein was run by SDS-PAGE on a 7.5% gel, and the separated proteins transferred to PVDF or nitrocellulose membranes. The membranes were probed with a rabbit polyclonal anti-mouse ACE antibody, and developed with an enhanced chemiluminescence kit from Amersham Corp. (21).…”

Section: Western Blotmentioning

confidence: 99%

The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice.

Esther¹,

Marino²,

Howard³

et al. 1997

J. Clin. Invest.

266

211

View full text Add to dashboard Cite

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“…In contrast, the germinal isozyme is unique to the testis, which expresses both isoenzymes at a ratio of 4:1(germinal:somatic) (Lanzillo et al, 1985). Transcription of testis ACE begins in late pachytene spermatocytes (Langford et al, 1993) or after meiosis (Sibony et al, 1994). The germinal isozyme is expressed exclusively in postmeiotic spermatogenic cells (late spermatids) and mature spermatozoa (Langford et al, 1993;Hagaman et al, 1998;Kohn et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Characterization of angiotensin-converting enzyme in canine testis

Sabeur¹,

Vo²,

Ball³

2001

Reproduction

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The aim of this study was to characterize angiotensin-converting enzyme (ACE) in canine testis. Detergent-extracted canine testes were sonicated in the presence of protease inhibitors and purified on an affinity column with the ACE inhibitor, lisinopril, as an affinity ligand for ACE. The fractions recovered were assessed for ACE enzyme activity via an enzyme kinetic microplate assay (at 330 nm) based on the hydrolysis of Fa-Phe-Gly-Gly (FAPGG) at pH 7.5 during an 8 min incubation. The specific activity of ACE in the starting testicular extracts was 3.53 +/- 0.99 mU mg(-1) protein with a 1588 times enrichment in ACE activity after lisinopril affinity chromatography (4239 +/- 2600 mU mg(-1) protein). The recovery efficiency of ACE after lisinopril affinity chromatography was 71.2%. The ACE activity in the detergent extracts and the purified fractions was inhibited significantly by 10 micromol captopril l(-1), a specific ACE inhibitor, and was restored to 88% of normal activity by the addition of the thiol-alkylating agent N-ethylmaleimide (0.5 mmol l(-1)) in the detergent extracts and the purified fractions incubated with captopril. The treatment of testicular extracts with 10 mmol EDTA l(-1) reduced the ACE activity significantly (5.40 +/- 1.26 versus 0.58 +/- 0.23 mU mg(-1)). The ACE activity was restored fully in the presence of zinc (5.28 +/- 0.70 mU mg(-1)). The anti-ACE antibody (raised against a 70 kDa protein from the periacrosomal plasma membrane of equine spermatozoa) recognized a 65-70 kDa protein in the detergent-extracted testes as well as in the affinity-purified fractions. This antibody also recognized a protein of similar molecular mass in ejaculated spermatozoa. ACE was localized in the periacrosomal area of the ejaculated spermatozoa and in spermatids in the seminiferous tubules. The results of this study demonstrate that ACE is present in canine testis and retains its enzyme activity after purification with lisinopril affinity chromatography. Activity of canine ACE is inhibited by captopril and EDTA and is restored in the presence of N-ethylmaleimide and zinc.

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“…Somatic ACE is expressed in vascular endothelial cells, kidney proximal tubules, intestinal brush border cells, macrophages, monocytes, and Leydig cells of the testes (7,32,33). Germinal ACE is expressed exclusively in maturing sperm cells (34). We have been examining the specific physiological roles played by ACE expressed in specific tissues.…”

mentioning

confidence: 99%

Maintenance of Normal Blood Pressure and Renal Functions Are Independent Effects of Angiotensin-converting Enzyme

Kessler

Senanayake

Scheidemantel

et al. 2003

Journal of Biological Chemistry

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Angiotensin-converting enzyme (ACE) is expressed in many tissues, including vasculature and renal proximal tubules, and its genetic ablation in mice causes abnormal renal structure and functions, hypotension, and male sterility. To test the hypothesis that specific physiological functions of ACE are mediated by its expression in specific tissues, we generated different mouse strains, each expressing ACE in only one tissue. Here, we report the properties of two such strains of mice that express ACE either in vascular endothelial cells or in renal proximal tubules. Because of the natural cleavage secretion process, both groups also have ACE in the serum. Both groups were as healthy as wild-type mice, having normal kidney structure and fluid homeostasis, though males remained sterile, because they lack ACE expression in sperm. Despite equivalent serum ACE and angiotensin II levels and renal functions, only the group that expressed ACE in vascular endothelial cells had normal blood pressure. Expression of ACE, either in renal proximal tubules or in vasculature, is sufficient for maintaining normal kidney functions. However, for maintaining blood pressure, ACE must be expressed in vascular endothelial cells. These results also demonstrate that ACE-mediated blood pressure maintenance can be dissociated from its role in maintaining renal structure and functions.

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Regulated Expression of Testis Angiotensin-Converting Enzyme during Spermatogenesis in Mice1

Cited by 87 publications

References 21 publications

The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice.

The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice.

Characterization of angiotensin-converting enzyme in canine testis

Maintenance of Normal Blood Pressure and Renal Functions Are Independent Effects of Angiotensin-converting Enzyme

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