Tags

Type your tag names separated by a space and hit enter

Functional analysis of a pancreatic secretory trypsin inhibitor-like protein in insects: silencing effects resemble the human pancreatic autodigestion phenotype.
Insect Biochem Mol Biol. 2011 Sep; 41(9):688-95.IB

Abstract

INTRODUCTION

In mammalian pancreatic cells, the pancreatic secretory trypsin inhibitor (PSTI) prevents the premature activation of digestive enzymes and thus plays an important role in a protective mechanism against tissue destruction by autophagy, a process which may ultimately cause diseases such as pancreatitis and pancreatic cancer. Insects, however, lack a pancreas and so far no PSTI-like peptides are functionally characterized.

RESULTS

In several insect species protease inhibitors that structurally resemble the mammalian PSTI were predicted in silico. A putative PSTI-like protein (LmPSTI) was cloned and sequenced in the African migratory locust, Locusta migratoria. For the first time the expression of an insect derived PSTI-like inhibitor was shown to be restricted to the digestive enzyme-producing organs in insects (midgut and caeca). LmPSTI was produced via a bacterial expression system and was found to be a potent inhibitor of bovine trypsin as well as endogenous locust gut enzymes. In the caeca, RNAi-mediated knockdown of LmPSTI resulted in a significantly upregulated expression (2-fold) of locust ATG8 transcripts (an ubiquitin-like protein crucial for autophagosome formation). These findings were confirmed by an ultrastructural study on caeca, revealing the presence of autophagy-related structures in RNAi-treated animals.

CONCLUSION

The results of this study lead us to believe that LmPSTI plays an important role in controlling the proteolytic activity in the digestive system of L. migratoria. These findings provide new evidence for the existence of an ancient protective mechanism in metazoan digestive systems and open new perspectives for the study of autophagy-related diseases in the digestive tract.

Authors+Show Affiliations

Department of Animal Physiology and Neurobiology, Zoological Institute K.U. Leuven, Naamsestraat 59, B-3000 Leuven, Belgium. Vincent.vanhoef@bio.kuleuven.beNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21571068

Citation

van Hoef, Vincent, et al. "Functional Analysis of a Pancreatic Secretory Trypsin Inhibitor-like Protein in Insects: Silencing Effects Resemble the Human Pancreatic Autodigestion Phenotype." Insect Biochemistry and Molecular Biology, vol. 41, no. 9, 2011, pp. 688-95.
van Hoef V, Breugelmans B, Spit J, et al. Functional analysis of a pancreatic secretory trypsin inhibitor-like protein in insects: silencing effects resemble the human pancreatic autodigestion phenotype. Insect Biochem Mol Biol. 2011;41(9):688-95.
van Hoef, V., Breugelmans, B., Spit, J., Simonet, G., Zels, S., Billen, J., & Vanden Broeck, J. (2011). Functional analysis of a pancreatic secretory trypsin inhibitor-like protein in insects: silencing effects resemble the human pancreatic autodigestion phenotype. Insect Biochemistry and Molecular Biology, 41(9), 688-95. https://doi.org/10.1016/j.ibmb.2011.04.012
van Hoef V, et al. Functional Analysis of a Pancreatic Secretory Trypsin Inhibitor-like Protein in Insects: Silencing Effects Resemble the Human Pancreatic Autodigestion Phenotype. Insect Biochem Mol Biol. 2011;41(9):688-95. PubMed PMID: 21571068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional analysis of a pancreatic secretory trypsin inhibitor-like protein in insects: silencing effects resemble the human pancreatic autodigestion phenotype. AU - van Hoef,Vincent, AU - Breugelmans,Bert, AU - Spit,Jornt, AU - Simonet,Gert, AU - Zels,Sven, AU - Billen,Johan, AU - Vanden Broeck,Jozef, Y1 - 2011/05/08/ PY - 2011/01/25/received PY - 2011/04/28/revised PY - 2011/04/29/accepted PY - 2011/5/17/entrez PY - 2011/5/17/pubmed PY - 2011/10/19/medline SP - 688 EP - 95 JF - Insect biochemistry and molecular biology JO - Insect Biochem Mol Biol VL - 41 IS - 9 N2 - INTRODUCTION: In mammalian pancreatic cells, the pancreatic secretory trypsin inhibitor (PSTI) prevents the premature activation of digestive enzymes and thus plays an important role in a protective mechanism against tissue destruction by autophagy, a process which may ultimately cause diseases such as pancreatitis and pancreatic cancer. Insects, however, lack a pancreas and so far no PSTI-like peptides are functionally characterized. RESULTS: In several insect species protease inhibitors that structurally resemble the mammalian PSTI were predicted in silico. A putative PSTI-like protein (LmPSTI) was cloned and sequenced in the African migratory locust, Locusta migratoria. For the first time the expression of an insect derived PSTI-like inhibitor was shown to be restricted to the digestive enzyme-producing organs in insects (midgut and caeca). LmPSTI was produced via a bacterial expression system and was found to be a potent inhibitor of bovine trypsin as well as endogenous locust gut enzymes. In the caeca, RNAi-mediated knockdown of LmPSTI resulted in a significantly upregulated expression (2-fold) of locust ATG8 transcripts (an ubiquitin-like protein crucial for autophagosome formation). These findings were confirmed by an ultrastructural study on caeca, revealing the presence of autophagy-related structures in RNAi-treated animals. CONCLUSION: The results of this study lead us to believe that LmPSTI plays an important role in controlling the proteolytic activity in the digestive system of L. migratoria. These findings provide new evidence for the existence of an ancient protective mechanism in metazoan digestive systems and open new perspectives for the study of autophagy-related diseases in the digestive tract. SN - 1879-0240 UR - https://www.unboundmedicine.com/medline/citation/21571068/Functional_analysis_of_a_pancreatic_secretory_trypsin_inhibitor_like_protein_in_insects:_silencing_effects_resemble_the_human_pancreatic_autodigestion_phenotype_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0965-1748(11)00101-9 DB - PRIME DP - Unbound Medicine ER -