Proteasome stress responses in Schistosoma mansoni

Abstract

The proteasome proteolytic system is the major ATP-dependent protease in eukaryotic cells responsible for intracellular protein turnover. Schistosoma mansoni has been reported to contain an ubiquitin-proteasome proteolytic pathway, and many studies have suggested a biological role of proteasomes in the development of this parasite. Additionally, evidence has suggested diversity in proteasome composition under several cellular conditions, and this might contribute to the regulation of its function in this parasite. The proteasomal system has been considered important to support the protein homeostasis during cellular stress. In this study, we described in vitro effects of oxidative stress, heat shock, and chemical stress on S. mansoni adults. Our findings showed that chemical stress induced with curcumin, IBMX, and MG132 modified the gene expression of the proteasomal enzymes SmHul5 and SmUbp6. Likewise, the expression of these genes was upregulated during oxidative stress and heat shock. Analyses of the S. mansoni life cycle showed differential gene expression in sporocysts, schistosomulae, and miracidia. These results suggested that proteasome accessory proteins participate in stress response during the parasite development. The expression level of SmHul5 and SmUbp6 was decreased by 16-fold and 9-fold, respectively, by the chemical stress induced with IBMX, which suggests proteasome disassembly. On the other hand, curcumin, MG132, oxidative stress, and heat shock increased the expression of these genes. Furthermore, the gene expression of maturation proteasome protein (SmPOMP) was increased in stress conditions induced by curcumin, MG132, and H₂O₂, which could be related to the synthesis of new proteasomes. S. mansoni adult worms were found to utilize similar mechanisms to respond to different conditions of stress. Our results demonstrated that oxidative stress, heat shock, and chemical stress modified the expression profile of genes related to the ubiquitin-proteasome system and suggested that the proteasome might be important in the cellular stress response in this parasite.

Curcumin Generates Oxidative Stress and Induces Apoptosis in Adult Schistosoma mansoni Worms

“…In previous studies, these primers had been used to verify the expression of the transcripts in adult S . mansoni worms incubated with CUR [38, 39]. To confirm the specificities of the primers, the PCR products were sequenced in the ABI 3100 automated sequencer (Applied Biosystems) by using a Dye Terminator kit.…”

Effects of proteasome inhibitor MG-132 on the parasite Schistosoma mansoni

“…In this way, our data suggest that under the inhibition caused by MG-132, treated parasites are engaged in the recovery of the proteasome function through the synthesis of new proteasome units. Similarly, De Paula et al [ 62 ] showed that different types of stress could drastically up-regulate the expression of two proteasome genes, namely SmHul5 and SmUbp6, suggesting that the proteasome is important in the cellular stress response in this parasite.…”

Schistosoma haematobium Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis

“…The proteasome is involved in the biogenesis of EVs [ 66 ] and also controls protein homeostasis and degradation of damaged proteins [ 67 ]. Furthermore, in schistosomes, the proteasome plays an important role in the cellular stress response and survival of the parasite [ 68 ]; it has been shown that treating mice with a proteasome inhibitor prior to infection with S. mansoni cercariae significantly impaired parasite development [ 69 ] and in vitro treatment of schistosomula with siRNAs targeting a deubiquitinase subunit of the 19S regulatory particle significantly reduced parasite viability [ 70 ].…”