title: Protective Effects of Emodin-Induced Neutrophil Apoptosis via the Ca2+-Caspase 12 Pathway against SIRS in Rats with Severe Acute Pancreatitis.
abstract: Severe acute pancreatitis (SAP) results in high mortality. This is partly because of early multiple organ dysfunction syndromes that are usually caused by systemic inflammatory response syndrome (SIRS). Many studies have reported the beneficial effects of emodin against SAP with SIRS. However, the exact mechanism underlying the effect of emodin remains unclear. This study was designed to explore the protective effects and underlying mechanisms of emodin against SIRS in rats with SAP. In the present study, cytosolic Ca2+levels, calpain 1 activity, and the expression levels of the active fragments of caspases 12 and 3 decreased in neutrophils from rats with SAP and increased after treatment with emodin. Delayed neutrophil apoptosis occurred in rats with SAP and emodin was able to reverse this delayed apoptosis and inhibit SIRS. The effect of emodin on calpain 1 activity, the expression levels of the active fragments of caspases 12 and 3, neutrophil apoptosis, and SIRS scores were attenuated by PD150606 (an inhibitor of calpain). These results suggest that emodin inhibits SIRS in rats with SAP by inducing circulating neutrophil apoptosis via the Ca2+-calpain 1-caspase 12-caspase 3 signaling pathway.
authors.affiliation: Pancreaticobiliary Centre, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Gui-Jun
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: Pancreaticobiliary Centre, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Integrative Medicine, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Teng
authors.affiliation: College of Integrative Medicine, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Fa-Lv
authors.initials: FL
authors.lastname: Sun
authors.affiliation: College of Integrative Medicine, Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xiang
authors.affiliation: Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Shi-Lin
authors.initials: SL
authors.lastname: Xia
authors.affiliation: Pancreaticobiliary Centre, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Gui-Xin
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: Pancreaticobiliary Centre, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Hai-Long
authors.identifier: 0000-0002-1101-1990
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Pancreaticobiliary Centre, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
authors.forename: Dong
authors.identifier: 0000-0003-1030-916X
authors.initials: D
authors.lastname: Shang
mesh_terms: D000179:Acrylates / Q000008:administration & dosage; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053454:Caspase 12 / Q000096:biosynthesis* / Q000235:genetics; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D004642:Emodin / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects; D010195:Pancreatitis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000179:Acrylates; C100442:PD 150606; D002154:Calpain; C000606071:Capn1 protein, rat; C506443:Casp12 protein, rat; D053454:Caspase 12; D053148:Caspase 3; D004642:Emodin; D002118:Calcium