Role of Calmodulin-Calmodulin Kinase II, cAMP/Protein Kinase A and ERK 1/2 on -Induced Apoptosis of Head Kidney Macrophages
Aeromonas hydrophila is a natural fish pathogen and is known to induce apoptosis of HKM. Head kidney is an important immune-organ in fish and HKM are critical for immunity against the invading pathogen. The mechanisms of cell death induced by A. hydrophila are incompletely characterized. We have studied the role of Ca2+-dependent signalling pathways in the induction of A. hydrophila-induced HKM apoptosis. We observed that A. hydrophila infection led to increased CaM expression in infected HKM which was Ca2+-dependent. The inhibitor and siRNA studies suggested CaM to be pro-apoptotic and triggered CaMKIIg expression in the infected HKM. Calpain-2 appeared to influence CaMKIIg expression. However, further studies are needed to understand the process. We report that the CaM-CaMKIIg pathway is important for initiating cAMP production within the infected HKM. The pro-apoptotic activation of cAMP dependent PKA was quite evident. The activation of ERK 1/2 was observed in the HKM and results clearly suggested the pro-active role of cAMP/PKA in the process. Thus we conclude that CaM-CaMKIIg initiates the cAMP/PKA pathway that induces ERK 1/2 phosphorylation to promote caspase-3 mediated apoptosis of the A. hydrophila-infected HKM.
Vyšlo v časopise:
Role of Calmodulin-Calmodulin Kinase II, cAMP/Protein Kinase A and ERK 1/2 on -Induced Apoptosis of Head Kidney Macrophages. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004018
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004018
Souhrn
Aeromonas hydrophila is a natural fish pathogen and is known to induce apoptosis of HKM. Head kidney is an important immune-organ in fish and HKM are critical for immunity against the invading pathogen. The mechanisms of cell death induced by A. hydrophila are incompletely characterized. We have studied the role of Ca2+-dependent signalling pathways in the induction of A. hydrophila-induced HKM apoptosis. We observed that A. hydrophila infection led to increased CaM expression in infected HKM which was Ca2+-dependent. The inhibitor and siRNA studies suggested CaM to be pro-apoptotic and triggered CaMKIIg expression in the infected HKM. Calpain-2 appeared to influence CaMKIIg expression. However, further studies are needed to understand the process. We report that the CaM-CaMKIIg pathway is important for initiating cAMP production within the infected HKM. The pro-apoptotic activation of cAMP dependent PKA was quite evident. The activation of ERK 1/2 was observed in the HKM and results clearly suggested the pro-active role of cAMP/PKA in the process. Thus we conclude that CaM-CaMKIIg initiates the cAMP/PKA pathway that induces ERK 1/2 phosphorylation to promote caspase-3 mediated apoptosis of the A. hydrophila-infected HKM.
Zdroje
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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