Related Experiment Videos
Complement C5b-9 membrane attack complex increases expression of endoplasmic reticulum stress proteins in glomerular
Andrey V Cybulsky1, Tomoko Takano, Joan Papillon
1Department of Medicine, McGill University Health Centre, Montreal, Quebec H3A 1A1, Canada. andrey.cybulsky@mcgill.ca
The Journal of Biological Chemistry
|August 23, 2002
Summary
Complement C5b-9 activates cytosolic phospholipase A(2) (cPLA(2)), damaging endoplasmic reticulum (ER) stress proteins in glomerular epithelial cells (GECs). Upregulated ER stress proteins protect against complement-mediated injury in membranous nephropathy.
Area of Science:
- Nephrology
- Cell Biology
- Immunology
Background:
- Membranous nephropathy involves glomerular epithelial cell (GEC) injury and proteinuria.
- Complement component C5b-9 is implicated in GEC injury and activation of cytosolic phospholipase A(2) (cPLA(2)).
- Endoplasmic reticulum (ER) stress proteins, such as bip and grp94, play roles in cellular injury.
Purpose of the Study:
- To investigate the role of ER stress proteins (bip, grp94) in complement-mediated GEC injury.
- To determine if cPLA(2) activation influences ER integrity and ER stress protein expression.
- To explore the protective potential of ER stress protein induction in the passive Heymann nephritis (PHN) model.
Main Methods:
- GECs overexpressing cPLA(2) and control GECs were incubated with complement.
- Leakage of bip and grp94 from ER to cytosol was measured to assess ER injury.
- mRNA and protein levels of bip and grp94 were analyzed after chronic complement exposure.
- Rats with PHN were analyzed for glomerular bip and grp94 expression.
- Rats were pretreated with tunicamycin or adriamycin to modulate ER stress protein levels.
Main Results:
- Complement-treated GECs overexpressing cPLA(2) showed greater bip and grp94 leakage, indicating compromised ER membrane integrity.
- Chronic complement exposure increased bip and grp94 mRNA and protein levels in a cPLA(2)-dependent manner.
- Reduced bip protein expression via antisense mRNA enhanced complement-dependent GEC injury.
- Glomerular bip and grp94 proteins were upregulated in proteinuric PHN rats.
- Pretreatment with tunicamycin or adriamycin reduced proteinuria in PHN.
Conclusions:
- Complement C5b-9 injures the ER and upregulates ER stress proteins, partly through cPLA(2) activation.
- ER stress protein induction represents a protective mechanism against complement-mediated kidney injury.
- This study reveals a novel role for ER stress proteins in mitigating membranous nephropathy.