title: Ameliorating ER-stress attenuates Aeromonas hydrophila-induced mitochondrial dysfunctioning and caspase mediated HKM apoptosis in Clarias batrachus.
abstract: Endoplasmic reticulum (ER)-stress and unfolding protein response (UPR) has not been implied in Aeromonas hydrophila-pathogenicity. We report increased expression of the ER-stress markers: CHOP, BiP and phospho-eIF2α in A. hydrophila-infected headkidney macrophages (HKM) in Clarias batrachus. Pre-treatment with ER-stress inhibitor, 4-PBA alleviated ER-stress and HKM apoptosis suggesting ER-UPR critical for the process. The ER-Ca(2+) released via inositol-triphosphate and ryanodine receptors induced calpain-2 mediated superoxide ion generation and consequent NF-κB activation. Inhibiting NF-κB activation attenuated NO production suggesting the pro-apoptotic role of NF-κB on HKM pathology. Calpain-2 activated caspase-12 to intensify the apoptotic cascade through mitochondrial-membrane potential (ψm) dissipation and caspase-9 activation. Altered mitochondrial ultra-structure consequent to ER-Ca(2+) uptake via uniporters reduced ψm and released cytochrome C. Nitric oxide induced the cGMP/PKG-dependent activation of caspase-8 and truncated-Bid formation. Both the caspases converge onto caspase-3 to execute HKM apoptosis. These findings offer a possible molecular explanation for A. hydrophila pathogenicity.
authors: Immunobiology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007, India.
authors: Chaitali
authors: C
authors: Banerjee
authors: Gut Biology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007, India.
authors: Ambika
authors: A
authors: Singh
authors: Department of Anatomy, All India Institute of Medical Sciences, Delhi 110 029, India.
authors: Taposh Kumar
authors: TK
authors: Das
authors: Gut Biology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007, India.
authors: Rajagopal
authors: R
authors: Raman
authors: Cell Signalling and Molecular Immunology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007, India.
authors: Anju
authors: A
authors: Shrivastava
authors: Immunobiology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007, India.
authors: Shibnath
authors: S
authors: Mazumder
mesh_terms: D016980:Aeromonas hydrophila / Q000472:pathogenicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002082:Butylamines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D053454:Caspase 12 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002397:Catfishes; D045304:Cytochromes c / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: C121358:4-phenylbutylamine; D002082:Butylamines; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D016328:NF-kappa B; D013481:Superoxides; D051742:Transcription Factor CHOP; D009569:Nitric Oxide; D045304:Cytochromes c; D002154:Calpain; D053454:Caspase 12; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D002118:Calcium