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Apoptosis is triggered by the cyclic AMP signalling pathway in renal mesangial cells
1Department of Pharmacology, Biozentrum, University of Basel, Basel, Switzerland.
Abstract:
Glomerular mesangial cells are regarded as specialized smooth muscle cells located within the renal glomeruli and fulfilling important functions in glomerular physiology and pathophysiology. Here, we report that activation of the cyclic AMP signalling pathway by dibutyryl cyclic AMP, forskolin, or the beta 2-adrenergic receptor agonist salbutamol results in induction of apoptosis in mesangial cells. Activation of the apoptotic programme results in DNA fragmentation which is visible for most forms of apoptosis and is paralleled by enrichment of cytosolic DNA/histone complexes, an increasing number of cellular 3'-OH-fragmented DNA ends and typical nuclear chromatin condensation. Induction of apoptosis was found to be dependent on translation and independent of nitric oxide synthase activity.
Insights
Activating the cyclic AMP pathway in glomerular mesangial cells induces apoptosis, a programmed cell death. This process involves DNA fragmentation and chromatin condensation, independent of nitric oxide synthase.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Biology
Background:
- Glomerular mesangial cells are vital for kidney function.
- Understanding their response to signaling pathways is crucial for renal pathophysiology.
Purpose of the Study:
- To investigate the effect of cyclic AMP (cAMP) pathway activation on mesangial cell apoptosis.
- To elucidate the molecular mechanisms underlying cAMP-induced apoptosis in these cells.
Main Methods:
- Treatment of mesangial cells with cAMP-activating agents (dibutyryl cyclic AMP, forskolin, salbutamol).
- Assessment of apoptosis markers: DNA fragmentation, DNA/histone complexes, 3'-OH DNA ends, and chromatin condensation.
- Evaluation of the role of translation and nitric oxide synthase (NOS) activity.
Main Results:
- Activation of the cAMP pathway robustly induced apoptosis in mesangial cells.
- Apoptosis was characterized by DNA fragmentation and nuclear condensation.
- The process was dependent on protein translation but not on nitric oxide synthase activity.
Conclusions:
- The cyclic AMP signaling pathway is a key regulator of apoptosis in glomerular mesangial cells.
- Targeting this pathway may offer therapeutic strategies for kidney diseases involving mesangial cell dysfunction.