Characterization of angiotensin converting enzyme in the African cotton leafworm Spodoptera littoralis : towards a role in growth and development

In humans, high blood pressure is an important risk factor for development of cardiovascular diseases. This explains the high interest in the factors that control blood pressure, thereby hoping to find reducing mechanisms. Angiotensin converting enzyme or ACE is involved in the regulation of the blood pressure through the renin-angiotensin system (RAS). It activates angiotensin I by converting it into the vasoconstrictive peptide angiotensin II and deactivates the vasodilator, bradykinin I, resulting in an increase in blood pressure (Erdos & Skidgel, 1987). ACE was first reported in 1956 (Skeggs et al., 1956). Since then, research on ACE and ACE inhibitors has been intensified. The discovery that orally applied ACE inhibitors was beneficial to patients suffering from a high blood pressure, is one of the major therapeutic advances of the last decade. ACE belongs to the M2 family of metallopeptidases. In general, a peptidase or protease (proteinase) is an enzyme that cleaves amino acid residues from peptides or proteins. Peptidases are classified in six major categories: aspartic peptidases, metallopeptidases, cysteine peptidases, serine peptidases, threonine peptidases and peptidases with an unknown catalytic function (Barret et al., 2004). ACE belongs to the zinc metallopeptidases, referring to the requirement of zinc for activity. This zinc ion interacts with the catalytic site of the peptidase through a zinc binding motif (HEXXH) that contains two histidine residues and a glutamic acid (E) as a third zinc ligand. ACE is an ancient enzyme. Recently, an ACE-like enzyme was characterized in the bacterial strain Xanthomonas axonopodis pv citri (Riviere et al., 2007). In invertebrates, it has been studied in most detail in the phylum of the Arthropoda, more specifically in the Hexapoda or insects. The evolutionary conservation of the enzyme does not necessarily imply a conservation of its physiological role. The ftrst insect ACE was described by Lamango & Isaac (1994) and its wide tissue distribution suggested it to be involved in several physiological processes. A role for insect ACE in blood pressure regulation is highly unlikely since insects have an open blood circulation system. In general, insect ACE is involved in the processing of regulatory peptides. These act as transmitters and modulators in the nervous system and as hormones controlling key physiological processes, behaviour and development. Studying the possible roles of ACE in invertebrates may lead to a greater understanding of the enzyme's impact in these organisms and may reveal conserved functions that remain unknown to date.