Evaluation of secretory activity in carp pancreatocytes (Cyprinus carpio L.) when using lactobacillus-based chelate and probiotic supplemental feed complexes

The experimental research was carried out on the juvenile carp (Cyprinus carpio L.). The impact from supplemental feeds consisting of variable concentrations of chelate compounds, biogenic trace elements and probiotic lactobacillus-based product Bacillus subtilis VKPM B-2335 was evaluated. Optical and qualitative parameters of the lactobacillus base were studied in order to identify the major group of substances potentially able to influence the end result. The purpose of this research was to identify changes in the structure of the zymogen granules and their dimensions at which supplemental feeds produce a stimulating effect on the synthesis of zymogens in exogenous cells of the secretory part of pancreas. At the outcome of the study, for the first time, it was possible to prove that the integrated action of chelates and lactobacillus-based probiotics complemented each other. Metal chelate compounds contributed to enlargement of the zymogen granules, if compared to the control values. The bacterial products accelerated production of the zymogen granules in acinar cells diffusely located in carp hepatopancreas.

Glycoprotein 2 in health and disease: lifting the veil

In 2020, we discovered glycoprotein 2 (GP2) variants associated with pancreatic cancer susceptibility in a genome-wide association study involving the Japanese population. Individuals carrying a missense coding variant (rs78193826) in the GP2 gene resulting in a p.V432M substitution had an approximately 1.5-fold higher risk of developing pancreatic cancer than those without this variant. GP2 is expressed on the inner surface of zymogen granules in pancreatic acinar cells, which are responsible for the sorting, storage and secretion of digestive enzymes. Upon neuronal, hormonal, or other stimulation, GP2 is cleaved from the membrane of zymogen granules and then secreted into the pancreatic duct and intestinal lumen. While the functions of GP2 remain poorly understood, emerging evidence suggests that it plays an antibacterial role in the gastrointestinal tract after being secreted from pancreatic acinar cells. Impaired GP2 functions may facilitate the adhesion of bacteria to the intestinal mucosa. In this review article, we summarize the role of GP2 in health and disease, emphasizing its functions in the gastrointestinal tract, as well as genetic variations in the GP2 gene and their associations with disease susceptibility. We hope that its robust genetic associations with pancreatic cancer, coupled with its emerging role in gastrointestinal mucosal immunity, will spur renewed research interest in GP2, which has been understudied over the past 30 years compared with its paralog uromodulin (UMOD).

Molecular mechanisms of mammalian autophagy

The ubiquitin-proteasome pathway (UPP) and autophagy play integral roles in cellular homeostasis. As part of their normal life cycle, most proteins undergo ubiquitination for some form of redistribution, localization and/or functional modulation. However, ubiquitination is also important to the UPP and several autophagic processes. The UPP is initiated after specific lysine residues of short-lived, damaged or misfolded proteins are conjugated to ubiquitin, which targets these proteins to proteasomes. Autophagy is the endosomal/lysosomal-dependent degradation of organelles, invading microbes, zymogen granules and macromolecules such as protein, carbohydrates and lipids. Autophagy can be broadly separated into three distinct subtypes termed microautophagy, chaperone-mediated autophagy and macroautophagy. Although autophagy was once thought of as non-selective bulk degradation, advancements in the field have led to the discovery of several selective forms of autophagy. Here, we focus on the mechanisms of primary and selective mammalian autophagy pathways and highlight the current knowledge gaps in these molecular pathways.