Pancreatic secretory trypsin inhibitor: More than a trypsin inhibitor

Abstract

Kazal-type serine protease inhibitor is one of the most important and widely distributed protease inhibitor families. Pancreatic secretory trypsin inhibitor (PSTI), also known as serine protease inhibitor Kazal type I(SPINK1), binds rapidly to trypsin, inhibits its activity and is likely to protect the pancreas from prematurely activated trypsinogen. Therefore, it is an important factor in the onset of pancreatitis. Recent studies found that PSTI/SPINK1 is also involved in self-regulation of acinar cell phagocytosis, proliferation and growth of a variety of cell lines. In addition, it takes part in the response to inflammatory factor or injury and is highly related to adult type II citrullinemia.

Lack Of PRSS1 And SPINK1 Polymorphisms In Serbian Acute Pancreatitis Patients

“…SPINK1 is an acute phase protein, synthesized in the acinar cells of the pancreas together with PRSS1. Being a strong protease inhibitor, its main role is to prevent premature trypsinogen activation and pancreatic autodigestion by creating a covalent bond between its lysine residue at position 41 and the catalytic serine residue of trypsin (12,31,(47)(48)(49)(50). The SPINK1 coding gene is localized on chromosome 5 (5q32), and it consists of 4 exons spanning a region of approximately 7.5 kb (51).…”

Cloning and prokaryotic expression of rat homolog of Serpina3n and its expression change during liver regeneration

“…Furthermore, the upregulation of the Serpina3n homologous protein lagged slightly behind that of its mRNA, implying that the increased mRNA level of the Serpina3n homologue could partly account for the enhanced expression of the Serpina3n homologous protein. Certain serine protease inhibitory factors are upregulated at the priming stage of LR (Deng et al, 2009) and may participate in antagonizing inflammatory or acute phase reactions after PH, thus preventing further damage to the remnant liver (Marchbank et al, 2009;Wang and Xu, 2010a), which could represent a type of endogenous cell protection mechanism. In addition, some studies have demonstrated that serine protease inhibitory factors are involved in the regulation of serine protease activation after nerve injury or the regulation of hepatocyte growth factor after liver damage and then play a vital role in acute phase reactions after hepatectomy and balancing the LR process (Gesase and Kiyama, 2007;Jin, 2007).…”

Roles of Serine Protease Inhibitor Kazal type 1 (SPINK1) in Prostate Cancer

“…SPINK1, also known as pancreatic secretory trypsin inhibitor or tumor-associated trypsin inhibitor, encodes a 56 amino acid secreted peptide, which contains three disulfide bonds and a trypsin-specific binding site formed by Lys-Ile [4,5]. SPINK1 is usually with a signal peptide of approximately 20 amino acids at N-terminal.…”

“…Analysis of the human SPINK1 gene reveals that it is located on 5q32 containing approximately 7.5 kb and four exons. A 40 bp DNA fragment located between kb -3.84 and -3.80 carries the element responsible for both transcriptional activity and IL-6-induced gene expression [4]. SPINK1 was originally isolated from the pancreas and its primary function is inhibition of serine proteases, such as trypsin, in the pancreas and small intestines [6].…”

“…Additionally, inactivation of SPINK1 in the pancreas results in autophagy of exocrine pancreatic cells, suggesting that SPINK1 may be important in cell survival. In liver cells, expression of SPINK1 can be induced by Hepatitis B virus and protects liver cells from serine protenase dependent cellular apoptosis [4]. Collectively, SPINK1 appears to play an important role in both cell survival and prevention of apoptosis by several different pathways in normal tissues.…”