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10:23
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
Multiple caspases mediate acute renal cell apoptosis induced by bacterial cell wall components
Marlyn P Langford1, David J McGee, Kathy H Ta
1Department of Ophthalmology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA. mlangf@lsuhsc.edu
Renal Failure
|February 22, 2011
Summary
Bacterial cell wall components trigger kidney cell apoptosis in septic acute renal failure (ARF). Pan-caspase inhibitors show promise in preventing this renal cell death and septic ARF.
Area of Science:
- Nephrology
- Cell Biology
- Immunology
Background:
- The precise triggers for caspase-mediated apoptosis in kidney cells during septic acute renal failure (ARF) remain incompletely understood.
- Bacterial cell wall components are implicated in sepsis, but their direct nephrotoxic effects require further elucidation.
Purpose of the Study:
- To investigate the nephrotoxic effects of bacterial muropeptides, peptidoglycans, and lipopolysaccharides on rabbit kidney cells.
- To determine the role of caspases and apoptotic pathways in bacterial component-induced renal cell death.
Main Methods:
- Rabbit kidney cells were exposed to bacterial cell wall components.
- Apoptosis was assessed by measuring APOPercentage™ dye uptake, caspase activities, and DNA degradation using colorimetric and densitometric assays.
- The efficacy of caspase-specific and pan-caspase inhibitors in preventing apoptosis was evaluated.
Main Results:
- Bacterial components induced dose-dependent increases in APOPercentage™ dye uptake, caspase activities, and DNA degradation.
- Multiple caspases (1, 2, 3, 4, 8, 10, 12) were activated, suggesting the involvement of extrinsic, intrinsic, and ER stress pathways.
- Pan-caspase inhibitor Q-VD-OPh was significantly more effective than Z-VAD-FMK in inhibiting cell death and apoptosis.
Conclusions:
- Bacterial cell wall components induce apoptosis in renal cells through multiple caspase-mediated pathways.
- These findings support bacterial cell wall-induced apoptosis as a pathogenic mechanism in septic ARF.
- Early administration of pan-caspase inhibitors may offer a prophylactic strategy against septic ARF.
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