Mycoplasma hyorhinis upregulates calpastatin and inhibits calpain-dependent proteolysis in SH-SY5Y neuroblastoma cells.
Mycoplasmas often contaminate cultured cells, leading to alterations in cellular gene expression, protein synthesis, signal transduction and metabolic pathways. Mycoplasmal contamination is often unnoticed, so that mycoplasma-induced alterations in cell functions may not be appreciated, unless specifically studied. Here, we show for the first time that contamination of SH-SY5Y cells by Mycoplasma hyorhinis leads to increased levels of calpastatin (the endogenous inhibitor of the Ca(2+)-dependent protease calpain), resulting in inhibition of Ca(2+)-induced calpain activation and inhibition of calpain-promoted proteolysis in the mycoplasmal-infected cells. Calpain activity is recovered upon calpastatin removal from extracts of contaminated cells. The calpain-calpastatin system has been implicated in a variety of physiological and pathological processes (signal transduction, motility, cell cycle, cell differentiation, membrane damage and apoptosis). Because the ratio of calpastatin to calpain is an important factor in the control of calpain activity within the cell, the elevated calpastatin may protect the mycoplasma-infected cells against certain types of damage (e.g. caused by high Ca(2+)). Thus, our results are important for studies on the modulation of host cells by mycoplasmas, and relevant to the pathobiology of processes involving mycoplasmal infections. The mycoplasma-infected cells provide a system for identifying factors that participate in the regulation of cellular calpastatin.
Elkind
Esther
E
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel.
Rechnitzer
Hagai
H
Vaisid
Tali
T
Kornspan
Jonathan D
JD
Barnoy
Sivia
S
Rottem
Shlomo
S
Kosower
Nechama S
NS
D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D002454:Cell Differentiation; D004866:Equipment Contamination; D054884:Host-Pathogen Interactions; D045790:Mycoplasma hyorhinis / Q000378:metabolism / Q000472:pathogenicity*; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D002135:Calcium-Binding Proteins; D011506:Proteins; C033668:calpastatin; D002154:Calpain; D002118:Calcium