How Is the Development of the Rat's Small Intestine Related to Changes in the Proteasome Pool?

This work aims to investigate how different periods of the early development of the rat's small intestine are associated with changes in the proteasome pool. By the 21st embryonic day (E21) and until the 30th day of postnatal development (P30), chymotrypsin-like and caspase-like activity of proteasomes, manifested by the subunits beta 5 + LMP7 and beta 1 + LMP2, respectively, as well as the individual activity of the immune subunits LMP7 and LMP2, changes on the background of a constant number of proteasomes. Moreover, both similar characteristics and differences in the dynamics of these types of activity were revealed. The similarities are as follows. Firstly, all the studied activity increases significantly after E18 and reaches a maximum at P5-P15. These changes correspond to the period of accelerated intestinal growth, colonization by its microbiota, development of adaptive processes, and digestive and immune functions. Secondly, there is a similarity in the decrease in all the studied types of activity by P22. The differences are as follows. Firstly, chymotrypsin-like and LMP7 activity decreases to a much lesser extent by P22 compared to caspase-like and LMP2 activity. Secondly, by P30 (the period of deprivation from the mother), only chymotrypsin-like and LMP7 activity increases again up to the maximum levels, which indicates its possible role in adaptation to external nutrition. The period of increased activity was accompanied by an increase in the proportion of activator PA28 alpha beta and immune proteasomes with LMP7 and/or LMP2 subunits in the total proteasome pool. The most significant jump in the content of immune subunits in the small intestine was detected at E21 and P0 (birthday, change in nutritional conditions). Thus, the additional development of immune proteasomes may be one of the factors contributing to a significant increase in activity in the perinatal period. Further development of the small intestine from P1 to P30 was accompanied by a less significant increase in the content of immune subunits. None of the studied types of activity and the number of proteasome subunits and activators at critical periods (E21, P0, P30) depended on the sex of rats. The activity of immune subunits was detected in several forms of proteasomes, 20S-19S, 20S-PA28 alpha beta and 20S, differing in the presence or absence of one or another activator. It can be assumed that multiple forms of immune proteasomes form biologically active peptides in several steps. Apparently, 20S-19S proteasomes containing immune subunits at the first stage produce smaller polypeptides with a specific structure from full-sized ubiquitinated proteins, which serve as substrates for 20S-PA28 alpha beta and/or 20S proteasomes. The latter probably form peptides at the final stage that are directly involved in intercellular interactions and the development of the immune function as well as in the adaptation to the microbiota and changing nutritional conditions.

Automated summary

This study aims to investigate the association between different periods of early rat's small intestine development and changes in the proteasome pool. The results showed that proteasome activity and immune subunit content increased during the period of accelerated growth, colonization by microbiota, and development of immune functions. However, the activity decreased during the weaning period and later stages of development. Additionally, the study found that immune proteasomes may contribute to the significant increase in activity during the perinatal period. The findings were not dependent on the sex of the rats.