Expression of Endoplasmic Reticulum Stress Associated Apoptosis Gene Caspase-12 in Lung of Paraquat-induced Pulmonary Fibrosis Rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZhangZhijian ¹ , DongYaoyao ¹ , WuCan ² , ShouYunfeng ³ , HeYouhu ⁴ ,  PengLibo ¹

1. Intensive Care Unit, Banan District People's Hospital, Chongqing, 401320, China;
2. ;
3. ;
4. ;

Corresponding author：

PengLibo, Email: plbbnicu@yeah.net

Keywords：

Paraquat; Pulmonary fibrosis; Endoplasmic reticulum stress; Apoptosis; Caspase-12

DOI：

10.7507/1671-6205.2014064

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the endoplasmic reticulum stress associated apoptosis gene Caspase-12 expression in paraquat-induced pulmonary fibrosis. Methods 30 adult healthy Sprague-Dawley(SD) rats were randomly divided into a nomal control group,two pulmonary fibrosis model groups (intragastrically administered paraquat for 14 days and 28 days,respectively).The model of pulmonary fibrosis was established through intragastrically administering paraquat at the dose of 30 mg/kg.RT-PCR was used to determine the mRNA expression of Caspase-12.Immunohistochemistry was used to determine the protein expression of Caspase-12.HE staining and Masson staining were used to determine the degree of alveolitis and pulmonary fibrosis. Results HE staining and Masson staining of lung tissues proved that pulmonary fibrosis model was successfully constructed.The degree of alveolitis and pulmonary fibrosis in the model group was significantly more serious than that in the control group(P<0.01).RT-PCR and Immunohistochemistry results showed that the expression of Caspase-12 were remarkably increased in the pulmonary fibrosis model group(14 d group)(P<0.01),even more elevated in 28 d group compared with the 14 d group. Conclusion The results demonstrate that the expression of Caspase-12 in paraquat poisoned rats is up-regulated,suggesting endoplasmic reticulum stress plays an important role in paraquat induced-pulmonary fibrosis.

Citation： ZhangZhijian, DongYaoyao, WuCan, ShouYunfeng, HeYouhu, PengLibo. Expression of Endoplasmic Reticulum Stress Associated Apoptosis Gene Caspase-12 in Lung of Paraquat-induced Pulmonary Fibrosis Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2014, 13(3): 268-272. doi: 10.7507/1671-6205.2014064 Copy

1.	Inokuchi Y,Nakajima Y,Shimazawa M,et al.Effect of an inducer of Bip,a molecular chaperone,on endoplasmic reticulum(ER) stress-in-duced retinal cell death.Invest Ophthalmol Vis Sci,2009,50:334-344.
2.	Dinis-Oliveira RJ,Duarte JA,Sánchez-Navarro A,et al.Paraquat poisonings:mechanisms of lung toxicity,clinical features,and treatment.Crit Rev Toxicol,2008,38:13-71.
3.	Dinis-Oliveira RJ,Sousa C,Remiao F,et al.Effects of sodium salicylate in the paraquat induced apoptotic events in rat lungs.Free Radical Biol Med,2007,43:48-61.
4.	Nakamura S,Lipton SA.Molecularmechanisms of nitrosative stress-mediated protein misfolding in neurodegen erative diseases.Cell Mol Life Sci,2007,64:1609-1620.
5.	Klintworth H,Newhouse K,Li T,et al.Activation of c-Jun N-Terminal protein kinase is a common mechanism underlying paraquat and rotenone induced dopaminergic cell apoptosis.Toxicol Sci,2007,97:149-162.
6.	张志坚,周从阳,罗雅娟,等.百草枯中毒大鼠肾组织Livin蛋白与Caspase-3的表达及干预.中华急诊医学杂志,2011,20:717-721.
7.	Zhang A,Zhang J,Sun P,et al.EIF2alpha and caspase-12 activation are involved in oxygen-glucose-serum deprivation/restoration-induced apoptosis of spinal cord astrccytes.Neurosci Lett,2010,478:32-36.
8.	张慧利,柳远飞,罗序睿,等.氢气饱和生理盐水对百草枯中毒大鼠肺组织的作用.中华急诊医学杂志,2011,20:708-711.
9.	Hubner RH,Gitter W,Mokhtari HE,et al.Standardized quantification of pulmonary fibrosis in histological samples.Biotechniques,2008,44:507-517.
10.	Yamashita M,Yamashita M,Ando Y.A long-term follow-up lung function in survivors of paraquat poisoning.Hum Exp Toxicol,2000,19:99-103.
11.	Ishida Y,Takayasu T,Kimura A,et al.Gene expression of cytokines and grouth factors in the lung after paraquat administration in mice.Leg Med,2006,8:102-109.
12.	Zhang C,Wang G,Zheng Z,et al.Endoplasmic reticulum-tethered transcription factor cAMP responsive element-binding protein,hepatocyte specific,regulates hepatic lipogenesis,fatty acid oxidation,and lipolysis upon metabolic stress in mice.Hepatology,2012,55:1070-1082.
13.	Satoh T,Abiru N,Kobayashi M,et al.CHOP deletion does not impact the development of diabetes but suppresses the early production of insulin autoantibody in the NOD mouse.Apoptosis,2011,16:438-448.
14.	Zhang K,Kaufman RJ.From endoplasmic-reticulum stress to the inflammatory response.Nature,2008,454:455-462.
15.	Nakagawa T,Zhu H,Morishima N,et al.Caspase-12 mediates ER-specific apoptosis and cytotoxicity by amyloid-beta.Nature,2000,403:98-103.
16.	Jung EJ,Avliyakulov NK,Boontheung P,et al.Pro-oxidative DRP chemicals induce heat shock proteins and an unfolding protein response in a bronchial epithelial cell line as determined by DIGE analysis.Protemics,2007,7:3906-3918.
17.	Kelaen SG,Duan X,Ji R,et al.Cigarette smoke induce an unfolded protein response in the human lung:a proteomic approach.Am J Respir Cell Mol Biol,2008,38:541-550.

1. Inokuchi Y,Nakajima Y,Shimazawa M,et al.Effect of an inducer of Bip,a molecular chaperone,on endoplasmic reticulum(ER) stress-in-duced retinal cell death.Invest Ophthalmol Vis Sci,2009,50:334-344.
2. Dinis-Oliveira RJ,Duarte JA,Sánchez-Navarro A,et al.Paraquat poisonings:mechanisms of lung toxicity,clinical features,and treatment.Crit Rev Toxicol,2008,38:13-71.
3. Dinis-Oliveira RJ,Sousa C,Remiao F,et al.Effects of sodium salicylate in the paraquat induced apoptotic events in rat lungs.Free Radical Biol Med,2007,43:48-61.
4. Nakamura S,Lipton SA.Molecularmechanisms of nitrosative stress-mediated protein misfolding in neurodegen erative diseases.Cell Mol Life Sci,2007,64:1609-1620.
5. Klintworth H,Newhouse K,Li T,et al.Activation of c-Jun N-Terminal protein kinase is a common mechanism underlying paraquat and rotenone induced dopaminergic cell apoptosis.Toxicol Sci,2007,97:149-162.
6. 张志坚,周从阳,罗雅娟,等.百草枯中毒大鼠肾组织Livin蛋白与Caspase-3的表达及干预.中华急诊医学杂志,2011,20:717-721.
7. Zhang A,Zhang J,Sun P,et al.EIF2alpha and caspase-12 activation are involved in oxygen-glucose-serum deprivation/restoration-induced apoptosis of spinal cord astrccytes.Neurosci Lett,2010,478:32-36.
8. 张慧利,柳远飞,罗序睿,等.氢气饱和生理盐水对百草枯中毒大鼠肺组织的作用.中华急诊医学杂志,2011,20:708-711.
9. Hubner RH,Gitter W,Mokhtari HE,et al.Standardized quantification of pulmonary fibrosis in histological samples.Biotechniques,2008,44:507-517.
10. Yamashita M,Yamashita M,Ando Y.A long-term follow-up lung function in survivors of paraquat poisoning.Hum Exp Toxicol,2000,19:99-103.
11. Ishida Y,Takayasu T,Kimura A,et al.Gene expression of cytokines and grouth factors in the lung after paraquat administration in mice.Leg Med,2006,8:102-109.
12. Zhang C,Wang G,Zheng Z,et al.Endoplasmic reticulum-tethered transcription factor cAMP responsive element-binding protein,hepatocyte specific,regulates hepatic lipogenesis,fatty acid oxidation,and lipolysis upon metabolic stress in mice.Hepatology,2012,55:1070-1082.
13. Satoh T,Abiru N,Kobayashi M,et al.CHOP deletion does not impact the development of diabetes but suppresses the early production of insulin autoantibody in the NOD mouse.Apoptosis,2011,16:438-448.
14. Zhang K,Kaufman RJ.From endoplasmic-reticulum stress to the inflammatory response.Nature,2008,454:455-462.
15. Nakagawa T,Zhu H,Morishima N,et al.Caspase-12 mediates ER-specific apoptosis and cytotoxicity by amyloid-beta.Nature,2000,403:98-103.
16. Jung EJ,Avliyakulov NK,Boontheung P,et al.Pro-oxidative DRP chemicals induce heat shock proteins and an unfolding protein response in a bronchial epithelial cell line as determined by DIGE analysis.Protemics,2007,7:3906-3918.
17. Kelaen SG,Duan X,Ji R,et al.Cigarette smoke induce an unfolded protein response in the human lung:a proteomic approach.Am J Respir Cell Mol Biol,2008,38:541-550.

Chinese Journal of Respiratory and Critical Care Medicine

Expression of Endoplasmic Reticulum Stress Associated Apoptosis Gene Caspase-12 in Lung of Paraquat-induced Pulmonary Fibrosis Rats

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content