Effect of CaMK <b>Ⅱ</b> expression regulation on liver function after liver transplantation in rats _CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 RAN Jianghua , ZHENG Kepu , LI Wang , ZHANG Xibing , LIU Boqiang , LI Wenkai

Department of Hepatobiliary and Pancreatic Vascular Surgery, Affiliated Calmette Hospital of Kunming Medical University (The First People's Hospital of Kunming), Kunming, Yunnan 650011, P.R.China;

Corresponding author：

RAN Jianghua, Email: rjh2u@163.com

Keywords：

calmodulin-dependent kinases casadesⅡ; liver transplantation; liver function; rat

DOI：

10.7507/1007-9424.201612040

Video：

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Objective To investigate the effect on expression regulation of calmodulin-dependent kinases casades (CaMK) Ⅱ on liver function after liver transplantation in rats. Methods Allogeneic orthotopic liver transplantation model was established by using the classic two-cuff method. The lentiviral expression systems of CaMKⅡγ protein and CaMKⅡγ shRNA were constructed. The lentiviral vector expressing CaMKⅡγ shRNA and the lentiviral vector expressing CaMKⅡγ protein were perfused into the rat after liver transplantation respectively, and the corresponding blank vector and normal saline were perfused into the control group at the same time. The serum levels of ALT and AST were measured at different time points of inferior vena cava blood in rats. Results The serum ALT and AST levels were debased in the after transplantation rats whose lentiviral vector expressing CaMKⅡγ shRNA (P<0.05). The serum ALT and AST levels were raised in the after transplantation rats whose lentiviral vector expressing CaMKⅡγ protein (P<0.05). There were no significant difference of serum ALT and AST levels between the blank control group and the saline group (P>0.05). Conclusion Specific blocking of CaMK Ⅱ signaling pathway can effectively reduce the serum ALT and AST levels after liver transplantation in rats, and enhanced CaMK Ⅱ signaling pathway increases the serum ALT and AST levels after liver transplantation in rats.

Citation： RAN Jianghua, ZHENG Kepu, LI Wang, ZHANG Xibing, LIU Boqiang, LI Wenkai. Effect of CaMK Ⅱ expression regulation on liver function after liver transplantation in rats . CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2017, 24(4): 438-442. doi: 10.7507/1007-9424.201612040 Copy

1.	Yamamoto H, Ohdan H, Shintaku S,et al. Role of the bcl-2/bax pathway in hepatocyte apoptosis during acute rejection after rat liver transplantation. Transpl Int, 1998, 11 Suppl 1: S179-S184.
2.	Wang Y, Tian Y, Ding Y,et al. MiR-152 may silence translation of CaMK Ⅱ and induce spontaneous immune tolerance in mouse liver transplantation. PloS One, 2014, 9(8): e105096.
3.	Kamada N, Calne RY. Orthotopic liver transplantation in the rat. Technique using cuff for portal vein anastomosis and biliary drainage. Transplantation, 1979, 28(1): 47-50.
4.	Miyata M, Fischer H, Fuhs M,et al. A simple method for orthotopic liver transplantation in the rat. Cuff technique for three vascular anastomoses. Transplantation, 1980, 30(5): 335-338.
5.	Klune JR, Tsung A. Molecular biology of liver ischemia/reperfusion injury: established mechanisms and recent advancements. Surg Clin North Am, 2010, 90(4): 665-677.
6.	Hao BB, Pan XX, Fan Y,et al. Oleanolic acid attenuates liver ischemia reperfusion injury by HO-1/Sesn2 signaling pathway. Hepatobiliary Pancreat Dis Int, 2016, 15(5): 519-524.
7.	Tapuria N, Junnarkar S, Abu-Amara M,et al. Haemoxygenase modulates cytokine induced neutrophil chemoattractant in hepatic ischemia reperfusion injury. World J Gastroenterol, 2016, 22(33): 7518-7535.
8.	Hori T, Gardner LB, Hata T,et al. Pretreatment of liver graftsin vivo by γ-aminobutyric acid receptor regulation reduces cold ischemia/warm reperfusion injury in rat. Ann Transplant, 2013, 18: 299-313.
9.	Shuh M, Bohorquez H, Cohen AJ,et al. Tumor necrosis factor-α: life and death of hepatocytes during liver ischemia/reperfusion injury. Ochsner J, 2013, 13(1): 119-130.
10.	Li Y, Jiang Z, Xue D,et al. Mycoplasma ovipneumoniae induces sheep airway epithelial cell apoptosis through an ERK signalling-mediated mitochondria pathway. BMC Microbiol, 2016, 16(1): 222-223.
11.	Pan Q, Xue M, Xiao SS,et al. A combination therapy with baicalein and taxol promotes mitochondria-mediated cell apoptosis: involving in Akt/β-catenin signaling pathway. DNA Cell Biol, 2016, 35(11): 646-656.
12.	Quijada P, Hariharan N, Cubillo JD,et al. Nuclear calcium/ calmodulin-dependent protein kinase Ⅱ signaling enhances cardiac progenitor cell survival and cardiac lineage commitment. J Biol Chem, 2015, 290(42): 25411-25426.
13.	Mukaida N, Wang YY, Li YY. Roles of Pim-3, a novel survival kinase, in tumorigenesis. Cancer Sci, 2011, 102(8): 1437-1442.
14.	Ha TT, Burwell ST, Goodwin ML,et al. Pleiotropic roles of Ca⁺²/calmodulin-dependent pathways in regulating cadmium-induced toxicity in human osteoblast-like cell lines. Toxicol Lett, 2016, 260: 18-27.
15.	Takeuchi M, Yamamoto T. Apoptosis induced by NAD depletion is inhibited by KN-93 in a CaMKⅡ-independent manner. Exp Cell Res, 2015, 335(1): 62-67.
16.	Zhu LJ, Klutho PJ, Scott JA,et al. Oxidative activation of the Ca²⁺/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) regulates vascular smooth muscle migration and apoptosis. Vascul Pharmacol, 2014, 60(2): 75-83.
17.	Wei JY, Lu QN, Li WM,et al. Intracellular translocation of histone deacetylase 5 regulates neuronal cell apoptosis. Brain Res, 2015, 16(4): 15-24.
18.	Lu H, Dong J, Zhang Y,et al. Pathological changes in primary cilia: A novel mechanism of graft cholangiopathy caused by prolonged cold preservation in a rat model of orthotopic liver transplantation. Biosci Trends, 2014, 8(4): 206-211.
19.	Banerjee C, Khatri P, Raman R,et al. Role of calmodulin-calmodulin kinase Ⅱ, cAMP/protein kinase A and ERK 1/2 on Aeromonas hydrophila-induced apoptosis of head kidney macrophages. PLoS Pathog, 2014, 10(4): e1004018.
20.	Roe ND, Ren J. Oxidative activation of Ca²⁺/calmodulin-activated kinase Ⅱ mediates ER stress-induced cardiac dysfunction and apoptosis. Am J Physiol Heart Circ Physiol, 2013, 304(6): H828-H839.
21.	Zhang C, Yang G, Lu D,et al. Expression of vascular endothelial growth factor and basic fibroblast growth factor in acute rejection reaction following rat orthotopic liver transplantation. Exp Ther Med, 2014, 8(2): 483-487.
22.	Chang H, Sheng JJ, Zhang L,et al. ROS-induced nuclear translocation of calpain-2 facilitates cardiomyocyte apoptosis in tail-suspended rats. J Cell Biochem, 2015, 116(10): 2258-2269.
23.	Bin-Dayel AF, Abdel Baky NA, Fadda LM,et al. Effect of aliskiren and carvedilol on expression of Ca²⁺/calmodulin-dependent protein kinase Ⅱ δ-subunit isoforms in cardiac hypertrophy rat model. Toxicol Mech Methods, 2016, 26(2): 122-131.
24.	Ling H, Gray CB, Zambon AC,et al. Ca²⁺/calmodulin-dependent protein kinase Ⅱ δ mediates myocardial ischemia/reperfusion injury through nuclear factor-κB. Circ Res, 2013, 112(6): 935-944.
25.	Moser MJ, Geiser JR, Davis TN. Ca²⁺-calmodulin promotes survival of pheromone-induced growth arrest by activation of calcineurin and Ca²⁺-calmodulin-dependent protein kinase. Mol Cell Biol, 1996, 16(9): 4824-4831.
26.	Schlegel A, Kron P, Graf R,et al. Warmvs. cold perfusion techniques to rescue rodent liver grafts. J Hepatol, 2014, 61(6): 1267-1275.

1. Yamamoto H, Ohdan H, Shintaku S,et al. Role of the bcl-2/bax pathway in hepatocyte apoptosis during acute rejection after rat liver transplantation. Transpl Int, 1998, 11 Suppl 1: S179-S184.
2. Wang Y, Tian Y, Ding Y,et al. MiR-152 may silence translation of CaMK Ⅱ and induce spontaneous immune tolerance in mouse liver transplantation. PloS One, 2014, 9(8): e105096.
3. Kamada N, Calne RY. Orthotopic liver transplantation in the rat. Technique using cuff for portal vein anastomosis and biliary drainage. Transplantation, 1979, 28(1): 47-50.
4. Miyata M, Fischer H, Fuhs M,et al. A simple method for orthotopic liver transplantation in the rat. Cuff technique for three vascular anastomoses. Transplantation, 1980, 30(5): 335-338.
5. Klune JR, Tsung A. Molecular biology of liver ischemia/reperfusion injury: established mechanisms and recent advancements. Surg Clin North Am, 2010, 90(4): 665-677.
6. Hao BB, Pan XX, Fan Y,et al. Oleanolic acid attenuates liver ischemia reperfusion injury by HO-1/Sesn2 signaling pathway. Hepatobiliary Pancreat Dis Int, 2016, 15(5): 519-524.
7. Tapuria N, Junnarkar S, Abu-Amara M,et al. Haemoxygenase modulates cytokine induced neutrophil chemoattractant in hepatic ischemia reperfusion injury. World J Gastroenterol, 2016, 22(33): 7518-7535.
8. Hori T, Gardner LB, Hata T,et al. Pretreatment of liver graftsin vivo by γ-aminobutyric acid receptor regulation reduces cold ischemia/warm reperfusion injury in rat. Ann Transplant, 2013, 18: 299-313.
9. Shuh M, Bohorquez H, Cohen AJ,et al. Tumor necrosis factor-α: life and death of hepatocytes during liver ischemia/reperfusion injury. Ochsner J, 2013, 13(1): 119-130.
10. Li Y, Jiang Z, Xue D,et al. Mycoplasma ovipneumoniae induces sheep airway epithelial cell apoptosis through an ERK signalling-mediated mitochondria pathway. BMC Microbiol, 2016, 16(1): 222-223.
11. Pan Q, Xue M, Xiao SS,et al. A combination therapy with baicalein and taxol promotes mitochondria-mediated cell apoptosis: involving in Akt/β-catenin signaling pathway. DNA Cell Biol, 2016, 35(11): 646-656.
12. Quijada P, Hariharan N, Cubillo JD,et al. Nuclear calcium/ calmodulin-dependent protein kinase Ⅱ signaling enhances cardiac progenitor cell survival and cardiac lineage commitment. J Biol Chem, 2015, 290(42): 25411-25426.
13. Mukaida N, Wang YY, Li YY. Roles of Pim-3, a novel survival kinase, in tumorigenesis. Cancer Sci, 2011, 102(8): 1437-1442.
14. Ha TT, Burwell ST, Goodwin ML,et al. Pleiotropic roles of Ca⁺²/calmodulin-dependent pathways in regulating cadmium-induced toxicity in human osteoblast-like cell lines. Toxicol Lett, 2016, 260: 18-27.
15. Takeuchi M, Yamamoto T. Apoptosis induced by NAD depletion is inhibited by KN-93 in a CaMKⅡ-independent manner. Exp Cell Res, 2015, 335(1): 62-67.
16. Zhu LJ, Klutho PJ, Scott JA,et al. Oxidative activation of the Ca²⁺/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) regulates vascular smooth muscle migration and apoptosis. Vascul Pharmacol, 2014, 60(2): 75-83.
17. Wei JY, Lu QN, Li WM,et al. Intracellular translocation of histone deacetylase 5 regulates neuronal cell apoptosis. Brain Res, 2015, 16(4): 15-24.
18. Lu H, Dong J, Zhang Y,et al. Pathological changes in primary cilia: A novel mechanism of graft cholangiopathy caused by prolonged cold preservation in a rat model of orthotopic liver transplantation. Biosci Trends, 2014, 8(4): 206-211.
19. Banerjee C, Khatri P, Raman R,et al. Role of calmodulin-calmodulin kinase Ⅱ, cAMP/protein kinase A and ERK 1/2 on Aeromonas hydrophila-induced apoptosis of head kidney macrophages. PLoS Pathog, 2014, 10(4): e1004018.
20. Roe ND, Ren J. Oxidative activation of Ca²⁺/calmodulin-activated kinase Ⅱ mediates ER stress-induced cardiac dysfunction and apoptosis. Am J Physiol Heart Circ Physiol, 2013, 304(6): H828-H839.
21. Zhang C, Yang G, Lu D,et al. Expression of vascular endothelial growth factor and basic fibroblast growth factor in acute rejection reaction following rat orthotopic liver transplantation. Exp Ther Med, 2014, 8(2): 483-487.
22. Chang H, Sheng JJ, Zhang L,et al. ROS-induced nuclear translocation of calpain-2 facilitates cardiomyocyte apoptosis in tail-suspended rats. J Cell Biochem, 2015, 116(10): 2258-2269.
23. Bin-Dayel AF, Abdel Baky NA, Fadda LM,et al. Effect of aliskiren and carvedilol on expression of Ca²⁺/calmodulin-dependent protein kinase Ⅱ δ-subunit isoforms in cardiac hypertrophy rat model. Toxicol Mech Methods, 2016, 26(2): 122-131.
24. Ling H, Gray CB, Zambon AC,et al. Ca²⁺/calmodulin-dependent protein kinase Ⅱ δ mediates myocardial ischemia/reperfusion injury through nuclear factor-κB. Circ Res, 2013, 112(6): 935-944.
25. Moser MJ, Geiser JR, Davis TN. Ca²⁺-calmodulin promotes survival of pheromone-induced growth arrest by activation of calcineurin and Ca²⁺-calmodulin-dependent protein kinase. Mol Cell Biol, 1996, 16(9): 4824-4831.
26. Schlegel A, Kron P, Graf R,et al. Warmvs. cold perfusion techniques to rescue rodent liver grafts. J Hepatol, 2014, 61(6): 1267-1275.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of CaMK Ⅱ expression regulation on liver function after liver transplantation in rats

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