Abstract
The activities of two classes of neutral proteases were studied: caspases and proteasomes, which could be contained in vesicles generated by human stem cells. The formation of apoptosomes could not be induced in human mesenchymal and hematopoietic stem cells (hereinafter—MSCs and HSCs, respectively) with the participation of cytochrome C. Caspase activity was found in the culture medium and in exosomes after the tumor necrosis factor α (TNFα) supplementation only. This activity is completely inhibited by a non-substrate caspase inhibitor emricane, and is not sensitive to proteasome inhibitors. It is assumed that this activity has a membrane and intracellular location. Supplementing of TNFα cell culture leads to the generation of neutrophils and other leukocytes and the formation of apoptosomes in them, which are secreted with the exosomes and remain circulating outside the cells. Extracellular activity pertains to protein complexes of molecular weight similar to 20S proteasomes and is probably represented by apoptosomes. It is suggested that TNFα induces in HSC culture the appearance of neutrophils or the generation of other differentiated cells that are capable of apoptosis, in contrast to HSCs or MSCs.
Highlights
The list of intercellular communicators has been supplemented by extracellular vesicles, whose content and membrane proteins are involved in cell signaling or its modulation [1]
We investigated the activities of two classes of neutral proteases: caspases and proteasomes, which could be contained in vesicles generated by adult human stem cells and which are involved in normal cell physiology, often determining the fate of cells and their very existence
Since the work is largely concerned to exosomes, the results are presented in the form of a comparison of the properties of exosomes isolated from MSC and hematopoietic stem cell MSC (HSC) cultures due to presence of sufficient information in the literature about exosomes from MSCs
Summary
The list of intercellular communicators has been supplemented by extracellular vesicles, whose content and membrane proteins are involved in cell signaling or its modulation [1]. It is known that white blood cells secrete exosomes containing proteasomes in the form of 20S particles [2]. It was found that the lack of Rpt, a protein in the regulatory subunit of proteasomes, leads to inactivation of muscle stem cell cells and their apoptosis [5]. The opposite example is ubiquitin-specific protease 7, which deubiquitinates proteasome targets and this prevents apoptosis of leukemic cells [6]. Proteasome inhibitors cause programmed death of myelogenous leukemia stem cells, “saving” p53 protein from proteolytic degradation, but do not cause apoptosis of HSCs, as they do not contain this protein in significant quantities required for the regulatory activity [7,8]
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