Abstract
Lysosomal serine carboxypeptidase Cathepsin A (CTSA) is a multifunctional enzyme with distinct protective and catalytic function. CTSA present in the lysosomal multienzyme complex to facilitate the correct lysosomal routing, stability and activation of with beta–galactosidase and alpha-neuraminidase. Beside CTSA has role in inactivation of bioactive peptides including bradykinin, substances P, oxytocin, angiotensin I and endothelin-I by cleavage of 1 or 2 amino acid(s) from C-terminal ends. In this study, we aimed to elucidate the regulatory role of CTSA on bioactive peptides in knock-in mice model of CTSAS190A. We investigated the level of bradykinin, substances P, oxytocin, angiotensin I and endothelin-I in the kidney, liver, lung, brain and serum from CTSAS190A mouse model at 3- and 6-months of age. Our results suggest CTSA selectively contributes to processing of bioactive peptides in different tissues from CTSAS190A mice compared to age matched WT mice.
Highlights
Lysosomal CathepsinA (CTSA), belonging to serine proteases family, is a multifunctional glycoprotein with three distinctive hydrolytic activities for deamidase, esterase and carboxypeptidase
In the concept of this study, we determined the level of five different endogenous bioactive peptides in kidney, liver, lung, brain and serum from CTSAS190A and WT male mice at 3- and 6months-old in order to reveal the importance of lysosomal Cathepsin A (CTSA) on the regulation of bioactive peptides in vivo
In 6 month old CTSAS190A mice’s kidney, the level of bradykinin, oxytocin and angiotensin-I were higher (1.3-fold, 1.2-fold and 1.5-fold, respectively) whereas substances P and endothelin-I levels were similar to age matching WT mice (Figure 1)
Summary
Lysosomal CathepsinA (CTSA), belonging to serine proteases family, is a multifunctional glycoprotein with three distinctive hydrolytic activities for deamidase, esterase and carboxypeptidase. It makes a complex with the two glycosidases, β-galactosidase (β-gal) and α–neuraminidase (Neu1) to protect them against proteolytic degradation in lysosome (reviewed in Bonten et al, 2014). CTSA is widely distributed but differentially expressed in human tissues with the highest expression in the distal and collecting tubular cells of kidney, epithelial cells of lung, liver and large neurons of brain (Satake et al, 1994; Sohma et al, 1999). The highest level expression of CTSA is observed in kidney, brain, liver and placenta (Galjart et al, 1990). Secreted to the blood plasma by platelets and lymphocytes, CTSA very likely plays an extralysosomal (cell membrane) and/or extracellular regulatory role for a variety of bioactive peptide hydrolyzing them (Jackman et al, 1990)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
