Angiotensin-converting enzyme as a target for the development of novel insect growth regulators

Isaac, R. Elwyn; Lamango, Nazarius S.; Ekbote, Uma V.; Taylor, Christopher L.; Hurst, Debra; Weaver, Robert J.; Çarhan, Ahmet; Burnham, Susan; Shirras, Alan D.

doi:10.1016/j.peptides.2006.08.029

Cited by 34 publications

(36 citation statements)

References 46 publications

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“…In this study, we thoroughly mixed 5 mg captopril with the Premix diet forcing the larvae to continuously ingest both the food and the ACE inhibitor. Isaac et al (2007) reported that injection of inhibitors was most effective when larvae had just molted into the fifth instar. In contrast to the feeding assay, where larvae gradually increase the amount of ingested ACE inhibitor, injection into newly molted larvae in our study led to a higher dose/weight ratio.…”

Section: Discussionmentioning

confidence: 99%

Effect of ace inhibitors and TMOF on growth, development, and trypsin activity of larval Spodoptera littoralis

Lemeire

Borovsky

Camp

et al. 2008

Arch Insect Biochem Physiol

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Angiotensin converting enzyme (ACE) is a zinc metallopeptidase capable of cleaving dipeptide or dipeptideamide moieties at the C-terminal end of peptides. ACE is present in the hemolymph and reproductive tissues of insects. The presence of ACE in the hemolymph and its broad substrate specificity suggests an important role in processing of bioactive peptides. This study reports the effects of ACE inhibitors on larval growth in the cotton leafworm Spodoptera littoralis. Feeding ACE inhibitors ad lib decreased the growth rate, inhibited ACE activity in the larval hemolymph, and down-regulated trypsin activity in the larval gut. These results indicate that S. littoralis ACE may influence trypsin biosynthesis in the larval gut by interacting with a trypsin-modulating oostatic factor (TMOF). Injecting third instar larvae with a combination of Aea-TMOF and the ACE inhibitor captopril, down-regulated trypsin biosynthesis in the larval gut indicating that an Aea-TMOF gut receptor analogue could be present. Injecting captopril and enalapril into newly molted fifth instar larvae stopped larval feeding and decreased weight gain. Together, these results indicate that ACE inhibitors are efficacious in stunting larval growth and ACE plays an important role in larval growth and development.

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Section: Discussionmentioning

confidence: 99%

Effect of ace inhibitors and TMOF on growth, development, and trypsin activity of larval Spodoptera littoralis

Lemeire

Borovsky

Camp

et al. 2008

Arch Insect Biochem Physiol

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“…arthropods and annelids) and even in some bacteria (Rawlings et al, 2006). In insects, ACE is a soluble secreted enzyme that is strongly expressed in the male reproductive tissues (Isaac et al, 2007). In the testes of Drosophila melanogaster, germ cells are the major site of ACE (known as ANCE) biosynthesis and male flies homozygous for hypomorphic alleles of Ance are infertile (Tatei et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Male accessory glands of Drosophila melanogaster make a secreted angiotensin I-converting enzyme (ANCE), suggesting a role for the peptide-processing enzyme in seminal fluid

Rylett

Walker

Howell

et al. 2007

Journal of Experimental Biology

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SUMMARY Angiotensin I-converting enzyme (ACE) expressed on the surface of endothelial cells is responsible for the last step in the synthesis of circulating angiotensin II and the inactivation of bradykinin. Mammalian ACE is also expressed in the prostate with other components of the renin–angiotensin system, and in developing spermatids, where the peptidase activity is known to be critical for normal sperm function. The importance of an ACE gene to male fertility has also been demonstrated in Drosophila melanogaster, where Ance is expressed in spermatids, and hypomorphic alleles of Ance cause a defect in spermiogenesis. Here we show that ANCE, which shares many enzymatic properties with mammalian ACE, is also a product of the male accessory gland of D. melanogaster. It is expressed in the secondary cells and is associated with the electron dense granule within the large vesicles of these cells. ACE proteolytic activity is lost from the accessory glands during mating,consistent with transfer to the mated female in the seminal fluid. The accessory gland ACE-like activity might have an evolutionarily conserved function processing biologically active peptides with a role in male fertility.

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“…High ACE activity in haemolymph has been shown for several insect species, like L. migratoria (Macours et al, 2003b), L. oleracea (Ekbote et al, 2003), M. sexta (Isaac et al, 2007) and S. littoralis (Lemeire et al, 2007) and confers to the processing of circulating peptide hormones by ACE (Lamango et al, 1997, Siviter et al, 2002b. Since ACE is not highly expressed in haemocytes of L. migratoria (Macours et al, 2003a) and S. littoralis (current paper), ACE circulating in the haemolymph must be secreted by other tissues.…”

Section: Article In Pressmentioning

confidence: 85%

“…Especially a role in vital physiological processes as reproduction and development (both embryogenesis and metamorphosis) has been determined Isaac et al, 2007). Reproductive tissues are a rich source of ACE.…”

Section: Introductionmentioning

confidence: 99%

“…The importance of ACE towards a successful metamorphosis is suggested by high ACE activities during last larval stage and early pupal stage in D. melanogaster and Lacanobia oleracea (Siviter et al, 2002b;Ekbote et al, 2003). Evidence from another view, studying the detrimental effect of ACE inhibitors like captopril and fosinopril on growth and development, has been shown for Spodoptera littoralis and Manduca sexta (Vercruysse et al, 2004;Isaac et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Angiotensin-converting enzyme in Spodoptera littoralis: Molecular characterization, expression and activity profile during development

Lemeire

Vanholme

Leeuwen

et al. 2008

Insect Biochemistry and Molecular Biology

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Angiotensin-converting enzyme as a target for the development of novel insect growth regulators

Cited by 34 publications

References 46 publications

Effect of ace inhibitors and TMOF on growth, development, and trypsin activity of larval Spodoptera littoralis

Effect of ace inhibitors and TMOF on growth, development, and trypsin activity of larval Spodoptera littoralis

Male accessory glands of Drosophila melanogaster make a secreted angiotensin I-converting enzyme (ANCE), suggesting a role for the peptide-processing enzyme in seminal fluid

Angiotensin-converting enzyme in Spodoptera littoralis: Molecular characterization, expression and activity profile during development

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