Objective To explore the regulating mechanism of hepatic injury in obstructive jaundice (OJ). Methods①Rat hepatocytes were isolated by in situ collagenase perfusion and primary culture. Hepatocytes were pretreated with various concentrations of protein kinase C (PKC) agonist parsmeae (PMA) and inhibitor chelerythrine for 20 min. After pretreatment, 50 μmol/L glycochenodeoxycholate (GCDC) was added. Cells were next detected by FCM and TUNEL.②Experimental obstructive jaundice was induced by double ligation of the bile duct (BDL), BDL for 3, 7, 14, 21days.We detected apoptotic status in liver with TUNEL and PKC protein in liver with immunohistochemistry method. Results①PMA increased GCDCinduced apoptosis and chelerythrine decreased GCDCinduced apoptosis in a concentrationdependent manner. ②The apoptotic rate of liver was related to time of OJ. Apoptosis index (AI) was the highest in 14day bile duct ligation. The ber PKC expression, the more number of apoptotic cells in OJ.Conclusion PKC takes part in the regulation and the occurrence and progression of hepatic injury in OJ.
Citation：
WANG Jianming,ZOU Shengquan. The Roles of Protein Kinase C Signal Pathway in the Occurrence and Development of Hepatic Injury in Obstructive Jaundice. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2002, 9(2): 76-79. doi:
Copy
Copyright © the editorial department of CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY of West China Medical Publisher. All rights reserved
| 1. |
Zhivotovsky B, Orrenius S, Brustugun OT, et al. Injected cytochrome C induces apoptosis [Ｊ]. Nature,1998; 391(6)∶449.
|
| 2. |
Ruiz MC, Izquierdo M, Murcia G, et al. Activation of protein kinase C attenuates early signals in tasmesiated apoptosis [Ｊ]. Eur J Immunol, 1997； 27(11)∶1442.
|
| 3. |
Spirey J,Bronk S, Gores GJ. GCDC induced lethal hepatocellular injury in rat hepatocytes. Role of ATP depletion and cytosolic free calcium [Ｊ]. J Clin Invest, 1993; 92(1)∶17.
|
| 4. |
Patel T, Bronk SF,Gores GF. Apoptosis and hepatobiliary disease [Ｊ]. Hepatology，1995; 21(9)∶1725.
|
| 5. |
Nishizuka Y, Szamel M, Resch K. The molecular heterogengeity of protein kinase C and its implication for cellular regulation [Ｊ]. Nature,1988; 334(7)∶661.
|
| 6. |
Blake A, Jones T,Rao Y, et al. Bile salt induced apoptosis of hepatocytes involves activation of protein kinase C [Ｊ]. Am J Physiol,1997; 272(5)∶1109.
|
| 7. |
Hannun YA, Bell RM. Rat brain protein C [Ｊ]. J Biol Chem,1990; 265(12)∶2962.
|
| 8. |
Slater SJ, Kelly MB, Taddeo FJ, et al. The modulation of protein kinase C activity by membrane lipid bilayer structure [Ｊ].J Biol Chem, 1994; 269(12)∶4866.
|
- 1. Zhivotovsky B, Orrenius S, Brustugun OT, et al. Injected cytochrome C induces apoptosis [Ｊ]. Nature,1998; 391(6)∶449.
- 2. Ruiz MC, Izquierdo M, Murcia G, et al. Activation of protein kinase C attenuates early signals in tasmesiated apoptosis [Ｊ]. Eur J Immunol, 1997； 27(11)∶1442.
- 3. Spirey J,Bronk S, Gores GJ. GCDC induced lethal hepatocellular injury in rat hepatocytes. Role of ATP depletion and cytosolic free calcium [Ｊ]. J Clin Invest, 1993; 92(1)∶17.
- 4. Patel T, Bronk SF,Gores GF. Apoptosis and hepatobiliary disease [Ｊ]. Hepatology，1995; 21(9)∶1725.
- 5. Nishizuka Y, Szamel M, Resch K. The molecular heterogengeity of protein kinase C and its implication for cellular regulation [Ｊ]. Nature,1988; 334(7)∶661.
- 6. Blake A, Jones T,Rao Y, et al. Bile salt induced apoptosis of hepatocytes involves activation of protein kinase C [Ｊ]. Am J Physiol,1997; 272(5)∶1109.
- 7. Hannun YA, Bell RM. Rat brain protein C [Ｊ]. J Biol Chem,1990; 265(12)∶2962.
- 8. Slater SJ, Kelly MB, Taddeo FJ, et al. The modulation of protein kinase C activity by membrane lipid bilayer structure [Ｊ].J Biol Chem, 1994; 269(12)∶4866.
