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Involvement of protein disulfide isomerase in subtilase cytotoxin-induced cell death in HeLa cells
- Source :
- Biochemical and biophysical research communications. 525(4)
- Publication Year :
- 2020
-
Abstract
- Subtilase cytotoxin (SubAB) is a member of bacterial AB5 toxin produced by certain enterohemorrhagic E. coli strains which cleaves host chaperone BiP in endoplasmic reticulum (ER), leading to ER stress-mediated cytotoxicity. Previous study suggested that protein disulfide isomerase (PDI), an enzyme which catalyzes the formation and breakage of disulfide bonds in proteins, regulates AB5 toxin such as cholera toxin by unfolding of A subunit, leading to its translocation into cytosol to induce disease. Although SubAB targets ER and has similar A subunit to that of other AB5 toxins, it is unclear whether PDI can modulate the SubAB function. Here we determined the role of PDI on SubAB-induced BiP cleavage, ER stress response and cytotoxicity in HeLa cells. We found that PDI knockdown significantly suppressed SubAB-induced BiP cleavage and eIF2α phosphorylation. The accumulation of SubAB in ER was perturbed upon PDI knockdown. Finally, cell viability assay showed that PDI knockdown and PDI inhibitor canceled the SubAB-induced cytotoxicity. Present results suggested that SubAB, after cellular uptake, translocates into ER and interacts with BiP that might be modulated by PDI. Identification of pivotal role of host proteins on bacterial toxin to elicit its pathogenesis is necessary basis for development of potential chemotherapy and new diagnostic strategy for control of toxin-producing bacterial infections.
- Subjects :
- inorganic chemicals
0301 basic medicine
Cell Survival
MAP Kinase Kinase 4
Protein subunit
Eukaryotic Initiation Factor-2
Biophysics
Protein Disulfide-Isomerases
medicine.disease_cause
Biochemistry
03 medical and health sciences
0302 clinical medicine
medicine
Humans
Subtilisins
Phosphorylation
RNA, Small Interfering
Protein disulfide-isomerase
Cytotoxicity
Molecular Biology
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
biology
Cell Death
Host Microbial Interactions
Chemistry
Endoplasmic reticulum
Escherichia coli Proteins
Cholera toxin
Cell Biology
AB5 toxin
Endoplasmic Reticulum Stress
nervous system diseases
Cell biology
body regions
Cytosol
030104 developmental biology
030220 oncology & carcinogenesis
Chaperone (protein)
Gene Knockdown Techniques
biology.protein
HeLa Cells
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 525
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....26af878b1959795b693734be80be4e9d