ROLE OF ENDOPLASMIC RETICULUM STRESS DURING MYOCARDIAL APOPTOSIS IN RATS WITH SEVEREBURN INJURY/_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CHU Wanli , CHAI Jiake , FENG Yongqiang , MA Li , HU Chao.

Department of Burns &;
Plastic, the First AffiliatedHospital of General Hospital of Chinese PLA, Beijing, 100048, P.R.China.;

Corresponding author：

Keywords：

Endoplasmic reticulum stress, Myocardium apoptosis, Burn injury, Rat

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Objective Endoplasmic reticulum stress (ERS) mediated apoptosis is one of the eukaryotic cellular
apoptotic pathways, to investigate the potential role of ERS during myocardium apoptosis in rats with severe burn
injury. Methods Sixty-four 7-week-old male Wistar rats, weighing 200-220 g, were randomly divided into 2 groups. Thirty
percentage of total body surface area full-thickness thermal injury was produced in 32 rats of burn group, while sham burn was
produced in 32 rats of control group. The heart tissues were harvested from 8 rats in each group at 1, 4, 7, and 14 days after burn
to observe the changes of myocardium ultrastructure with transmission electron microscope (TEM). Myocardium apoptosis was
detected with TUNEL assay. The expressions of glucose regulated protein 78 (GRP 78), C/EBP-homologous protein (CHOP),
and cleaved Caspase 12 in different pathways of ERS were analysed with Western blot. Results All rats survived during the
experiment. Apoptotic changes of cardiomyocytes were observed in burn group, and the apoptosis index in burn group was
significantly higher than that in control group at each time point (P lt; 0.05), and it reached peak at 7 days after burn injury
(P lt; 0.05). The expressions of myocardial GRP 78, CHOP, and cleaved Caspase 12 showed persistent elevation in burn group.
The expressions of GRP 78 and cleaved Caspase 12 in burn group were significantly higher than those in control group at each
time point (P lt; 0.05), while the expression of CHOP was higher than that in control group at the other time points (P lt; 0.05)
except 1st day after burn injury. Conclusion ERS and CHOP, Caspase 12 mediated apoptotic pathway are activated in
myocardium after severe burn injury, and this may be one pathway of myocardium apoptosis.

Citation： CHU Wanli,CHAI Jiake,FENG Yongqiang,MA Li,HU Chao.. ROLE OF ENDOPLASMIC RETICULUM STRESS DURING MYOCARDIAL APOPTOSIS IN RATS WITH SEVEREBURN INJURY/. Chinese Journal of Reparative and Reconstructive Surgery, 2012, 26(5): 592-596. doi: Copy

1.	c-independent activation of caspase-9 by caspase-12. J Biol Chem, 2002, 277(37): 34287-34294.
2.	Carlson DL, Horton JW. Cardiac molecular signaling after burn trauma. J Burn Care Res, 2006, 27(5): 669-675.
3.	Rasheva VI, Domingos PM. Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis, 2009, 14(8): 996-1007.
4.	Rao RV, Ellerby HM, Bredesen DE. Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ, 2004, 11(4): 372-380.
5.	蔡建华, 柴家科, 申传安, 等. 烧伤、冲击伤及烧冲复合伤后大鼠早期血清中性粒细胞弹性蛋白酶的变化及意义. 中华医学杂志, 2010, 90(24): 1707-1710.
6.	Zhang JP, Ying X, Liang WY, et al. Apoptosis in cardiac myocytes during the early stage after severe burn. J Trauma, 2008, 65(2): 401-408.
7.	张西联, 黄跃生, 党永明, 等. 生脉注射液对大鼠烧伤后心肌细胞凋亡的影响. 第三军医大学学报, 2007, 29(2): 94-96.
8.	万义福, 许宝华, 张玉珍, 等. 大鼠严重烧伤后心肌细胞GRP94表达变化及其意义. 中国比较医学杂志, 2008, 18(2): 43-47.
9.	柴家科, 盛志勇. 进一步重视大面积深度烧伤皮肤替代物的研究. 中华烧伤杂志, 2002, 18(2): 73-74.
10.	Williams FN, Herndon DN, Suman OE, et al. Changes in cardiac physiology after severe burn injury. J Burn Care Res, 2011, 32(2): 269-274.
11.	George I, Sabbah HN, Xu K, et al. β-adrenergic receptor blockade reduces endoplasmic reticulum stress and normalizes calcium handling in a coronary embolization model of heart failure in canines. Cardiovasc Res, 2011, 91(3): 447-455.
12.	Tao J, Zhu W, Li Y, et al. Apelin-13 protects the heart against ischemia-reperfusion injury through inhibition of ER-dependent apoptotic pathways in a time-dependent fashion. Am J Physiol Heart Circ Physiol, 2011, 301(4): H1471-1486.
13.	Xin W, Li X, Lu X, et al. Involvement of endoplasmic reticulum stress-associated apoptosis in a heart failure model induced by chronic myocardial ischemia. Int J Mol Med, 2011, 27(4): 503-509.
14.	Sari FR, Widyantoro B, Thandavarayan RA, et al. Attenuation of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice. Cell Physiol Biochem, 2011, 27(5): 487-496.
15.	Yin XL, Zhang W, Yang Y, et al. Increasing expression of (CCAAT enhancer binding protein) homologous protein induced by endoplasmic reticulum stress in myocardium after cardiac arrest and resuscitation in rat. Resuscitation, 2012, 83(3): 378-385.
16.	Chen S, Du J, Liang Y, et al. Sulfur dioxide inhibits excessively activated endoplasmic reticulum stress in rats with myocardial injury. Heart Vessels, 2011. [Epub ahead of print].
17.	Minamino T, Komuro I, Kitakaze M. Endoplasmic reticulum stress as a therapeutic target in cardiovascular disease. Circ Res, 2010, 107(9): 1071-1082.
18.	Zang Q, Maass DL, White J, et al. Cardiac mitochondrial damage and loss of ROS defense after burn injury: the beneficial effects of antioxidant therapy. J Appl Physiol, 2007, 102(1): 103-112.
19.	Groenendyk J, Sreenivasaiah PK, Kim do H, et al. Biology of endoplasmic reticulum stress in the heart. Circ Res, 2010, 107(10): 1185-1197.
20.	Wu T, Dong Z, Geng J, et al. Valsartan protects against ER stress-induced myocardial apoptosis via CHOP/Puma signaling pathway in streptozotocin-induced diabetic rats. Eur J Pharm Sci, 2011, 42(5): 496-502.
21.	Ballard-Croft C, Carlson D, Maass DL, et al. Burn trauma alters calcium transporter protein expression in the heart. J Appl Physiol, 2004, 97(4): 1470-1476.
22.	Morishima N, Nakanishi K, Takenouchi H, et al. An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome.

1. c-independent activation of caspase-9 by caspase-12. J Biol Chem, 2002, 277(37): 34287-34294.
2. Carlson DL, Horton JW. Cardiac molecular signaling after burn trauma. J Burn Care Res, 2006, 27(5): 669-675.
3. Rasheva VI, Domingos PM. Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis, 2009, 14(8): 996-1007.
4. Rao RV, Ellerby HM, Bredesen DE. Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ, 2004, 11(4): 372-380.
5. 蔡建华, 柴家科, 申传安, 等. 烧伤、冲击伤及烧冲复合伤后大鼠早期血清中性粒细胞弹性蛋白酶的变化及意义. 中华医学杂志, 2010, 90(24): 1707-1710.
6. Zhang JP, Ying X, Liang WY, et al. Apoptosis in cardiac myocytes during the early stage after severe burn. J Trauma, 2008, 65(2): 401-408.
7. 张西联, 黄跃生, 党永明, 等. 生脉注射液对大鼠烧伤后心肌细胞凋亡的影响. 第三军医大学学报, 2007, 29(2): 94-96.
8. 万义福, 许宝华, 张玉珍, 等. 大鼠严重烧伤后心肌细胞GRP94表达变化及其意义. 中国比较医学杂志, 2008, 18(2): 43-47.
9. 柴家科, 盛志勇. 进一步重视大面积深度烧伤皮肤替代物的研究. 中华烧伤杂志, 2002, 18(2): 73-74.
10. Williams FN, Herndon DN, Suman OE, et al. Changes in cardiac physiology after severe burn injury. J Burn Care Res, 2011, 32(2): 269-274.
11. George I, Sabbah HN, Xu K, et al. β-adrenergic receptor blockade reduces endoplasmic reticulum stress and normalizes calcium handling in a coronary embolization model of heart failure in canines. Cardiovasc Res, 2011, 91(3): 447-455.
12. Tao J, Zhu W, Li Y, et al. Apelin-13 protects the heart against ischemia-reperfusion injury through inhibition of ER-dependent apoptotic pathways in a time-dependent fashion. Am J Physiol Heart Circ Physiol, 2011, 301(4): H1471-1486.
13. Xin W, Li X, Lu X, et al. Involvement of endoplasmic reticulum stress-associated apoptosis in a heart failure model induced by chronic myocardial ischemia. Int J Mol Med, 2011, 27(4): 503-509.
14. Sari FR, Widyantoro B, Thandavarayan RA, et al. Attenuation of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice. Cell Physiol Biochem, 2011, 27(5): 487-496.
15. Yin XL, Zhang W, Yang Y, et al. Increasing expression of (CCAAT enhancer binding protein) homologous protein induced by endoplasmic reticulum stress in myocardium after cardiac arrest and resuscitation in rat. Resuscitation, 2012, 83(3): 378-385.
16. Chen S, Du J, Liang Y, et al. Sulfur dioxide inhibits excessively activated endoplasmic reticulum stress in rats with myocardial injury. Heart Vessels, 2011. [Epub ahead of print].
17. Minamino T, Komuro I, Kitakaze M. Endoplasmic reticulum stress as a therapeutic target in cardiovascular disease. Circ Res, 2010, 107(9): 1071-1082.
18. Zang Q, Maass DL, White J, et al. Cardiac mitochondrial damage and loss of ROS defense after burn injury: the beneficial effects of antioxidant therapy. J Appl Physiol, 2007, 102(1): 103-112.
19. Groenendyk J, Sreenivasaiah PK, Kim do H, et al. Biology of endoplasmic reticulum stress in the heart. Circ Res, 2010, 107(10): 1185-1197.
20. Wu T, Dong Z, Geng J, et al. Valsartan protects against ER stress-induced myocardial apoptosis via CHOP/Puma signaling pathway in streptozotocin-induced diabetic rats. Eur J Pharm Sci, 2011, 42(5): 496-502.
21. Ballard-Croft C, Carlson D, Maass DL, et al. Burn trauma alters calcium transporter protein expression in the heart. J Appl Physiol, 2004, 97(4): 1470-1476.
22. Morishima N, Nakanishi K, Takenouchi H, et al. An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome.

Chinese Journal of Reparative and Reconstructive Surgery

ROLE OF ENDOPLASMIC RETICULUM STRESS DURING MYOCARDIAL APOPTOSIS IN RATS WITH SEVEREBURN INJURY/

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