Research on mechanism of hydrogen sulfide in regulating autophagy to protect organ dysfunction in sepsis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

NIE Jingyun ¹ , KANG Fugui ¹ , ZHANG Chenhan ¹ ,  CHAI Chen ^1,2

1. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China;
2. Department of General Surgery, People’s Hospital of Suzhou New District, Suzhou, Jiangsu 215000, P. R. China;

Corresponding author：

CHAI Chen, Email: chasechai@126.com

Keywords：

sepsis; organ dysfunction; autophagy; hydrogen sulfide; signal pathway

DOI：

10.7507/1007-9424.202005059

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the mechanism of hydrogen sulfide (H₂S) in regulating autophagy and ameliorating multi-organ dysfunction in the treatment of sepsis.Method The relevant literatures at home and abroad in recent years were systematically searched and read to review the mechanism of H₂S in regulating autophagy and ameliorating multi-organ dysfunction during sepsis.Results As a new medical gas signal molecule, H₂S could regulate autophagy by regulating multiple signal pathways such as Nrf2, NF-κB, MAPK, AMPK, etc., then ameliorated multi-organ dysfunction in sepsis.Conclusion H₂S inhibits inflammation, oxidative stress, and apoptosis by regulating autophagy, thus ameliorating multi-organ dysfunction in sepsis, which is expected to become an effective therapeutic target for sepsis.

Citation： NIE Jingyun, KANG Fugui, ZHANG Chenhan, CHAI Chen. Research on mechanism of hydrogen sulfide in regulating autophagy to protect organ dysfunction in sepsis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(2): 260-264. doi: 10.7507/1007-9424.202005059 Copy

1.	Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA, 2016, 315(8): 801-810.
2.	Xie J, Wang H, Kang Y, et al. The epidemiology of sepsis in Chinese ICUs: A national cross-sectional survey. Crit Care Med, 2020, 48(3): e209-e218.
3.	Huang M, Cai SL, Su JQ. The pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci, 2019, 20(21): 5376.
4.	Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Crit Care Med, 2018, 46(6): 997-1000.
5.	Feng Y, Liu B, Zheng X, et al. The protective role of autophagy in sepsis. Microb Pathog, 2019, 131: 106-111.
6.	Yin X, Xin H, Mao S, et al. The role of autophagy in sepsis: protection and injury to organs. Front Physiol, 2019, 10: 1071.
7.	Chen Y, Jin S, Teng X, et al. Hydrogen sulfide attenuates LPS-induced acute kidney injury by inhibiting inflammation and oxidative stress. Oxid Med Cell Longev, 2018, 2018: 6717212.
8.	Jiang L, Jiang Q, Yang S, et al. GYY4137 attenuates LPS-induced acute lung injury via heme oxygenase-1 modulation. Pulm Pharmacol Ther, 2019, 54: 77-86.
9.	Wu D, Wang H, Teng T, et al. Hydrogen sulfide and autophagy: A double edged sword. Pharmacol Res, 2018, 131: 120-127.
10.	Qiu P, Liu Y, Zhang J. Review: the role and mechanisms of macrophage autophagy in sepsis. Inflammation, 2019, 42(1): 6-19.
11.	Watanabe E, Thampy LK, Hotchkiss RS. Immunoadjuvant therapy in sepsis: novel strategies for immunosuppressive sepsis coming down the pike. Acute Med Surg, 2018, 5(4): 309-315.
12.	Hsu C. Autophagy: A potential target for rescuing sepsis-induced hepatic failure. Chin J Physiol, 2019, 62(2): 53-62.
13.	Li Y, Wang F, Luo Y. Ginsenoside Rg1 protects against sepsis-associated encephalopathy through beclin 1-independent autophagy in mice. J Surg Res, 2017, 207: 181-189.
14.	Zhao Y, Feng X, Li B, et al. Dexmedetomidine protects against lipopolysaccharide-induced acute kidney injury by enhancing autophagy through inhibition of the PI3K/AKT/mTOR pathway. Front Pharmacol, 2020, 11: 128.
15.	Yuan X, Chen G, Guo D, et al. Polydatin alleviates septic myocardial injury by promoting SIRT6-mediated autophagy. Inflammation, 2020, 43(3): 785-795.
16.	Hu J, Shi Y, Wang C, et al. Role of intestinal trefoil factor in protecting intestinal epithelial cells from burn-induced injury. Sci Rep, 2018, 8(1): 3201.
17.	Park SY, Shrestha S, Youn YJ, et al. Autophagy primes neutrophils for neutrophil extracellular trap formation during sepsis. Am J Respir Crit Care Med, 2017, 196(5): 577-589.
18.	Shao Y, Chen F, Chen Y, et al. Association between genetic polymorphisms in the autophagy-related 5 gene promoter and the risk of sepsis. Sci Rep, 2017, 7(1): 9399.
19.	Huang YY, Zhou F, Shen C, et al. LBP reduces the inflammatory injuryof kidney in septic rat and regulates the Keap1-Nrf2∕ARE signaling pathway1. Acta Cir Bras, 2019, 34(1): e20190010000003.
20.	Ahmed SM, Luo L, Namani A, et al. Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis, 2017, 1863(2): 585-597.
21.	Wen Z, Liu W, Li X, et al. A protective role of the NRF2-Keap1 pathway in maintaining intestinal barrier function. Oxid Med Cell Longev, 2019, 2019: 1759149.
22.	Liao W, Wang Z, Fu Z, et al. p62/SQSTM1 protects against cisplatin-induced oxidative stress in kidneys by mediating the cross talk between autophagy and the Keap1-Nrf2 signalling pathway. Free Radic Res, 2019, 53(7): 800-814.
23.	Zhao S, Song T, Gu Y, et al. Hydrogen sulfide alleviates liver injury via S-sulfhydrated-Keap1/Nrf2/LRP1 pathway. Hepatology, 2020: [Online ahead of print.
24.	Wu JC, Tian ZL, Sun Y, et al. Exogenous H2S facilitating ubiquitin aggregates clearance via autophagy attenuates type 2 diabetes-induced cardiomyopathy. Cell Death Dis, 2017, 8(8): e2992.
25.	Xiao Z, Liu L, Tao W, et al. Clostridium tyrobutyricum protect intestinal barrier function from LPS-induced apoptosis via P38/JNK signaling pathway in IPEC-J2 cells. Cell Physiol Biochem, 2018, 46(5): 1779-1792.
26.	Dong N, Xu X, Xue C, et al. Ethyl pyruvate inhibits LPS induced IPEC-J2 inflammation and apoptosis through p38 and ERK1/2 pathways. Cell Cycle, 2019, 18(20): 2614-2628.
27.	Zhu W, Lu Q, Wan L, et al. Sodium tanshinone ⅡA sulfonate ameliorates microcirculatory disturbance of small intestine by attenuating the production of reactie oxygen species in rats with sepsis. Chin J Integr Med, 2016, 22(10): 745-751.
28.	Zhou M, Xu W, Wang J, et al. Boosting mTOR-dependent autophagy via upstream TLR4-MyD88-MAPK signalling and downstream NF-κB pathway quenches intestinal inflammation and oxidative stress injury. EBioMedicine, 2018, 35: 345-360.
29.	He Y, She H, Zhang T, et al. p38 MAPK inhibits autophagy and promotes microglial inflammatory responses by phosphorylating ULK1. J Cell Biol, 2018, 217(1): 315-328.
30.	Schwartz M, Böckmann S, Borchert P, et al. SB202190 inhibits endothelial cell apoptosis via induction of autophagy and heme oxygenase-1. Oncotarget, 2018, 9(33): 23149-23163.
31.	Zhang GY, Lu D, Duan SF, et al. Hydrogen sulfide alleviates lipopolysaccharide-induced diaphragm dysfunction in rats by reducing apoptosis and inflammation through ROS/MAPK and TLR4/NF-kappaB signaling pathways. Oxid Med Cell Longev, 2018, 2018: 9647809.
32.	Han X, Mao Z, Wang S, et al. GYY4137 protects against MCAO via p38 MAPK mediated anti-apoptotic signaling pathways in rats. Brain Res Bull, 2020, 158: 59-65.
33.	Zhu MJ, Sun X, Du M. AMPK in regulation of apical junctions and barrier function of intestinal epithelium. Tissue Barriers, 2018, 6(2): 1-13.
34.	Kitzmiller L, Ledford JR, Hake PW, et al. Activation of AMP-activated protein kinase by A769662 ameliorates sepsis-induced acute lung injury in adult mice. Shock, 2019, 52(5): 540-549.
35.	Shimizu Y, Polavarapu R, Eskla KL, et al. Hydrogen sulfide regulates cardiac mitochondrial biogenesis via the activation of AMPK. J Mol Cell Cardiol, 2018, 116: 29-40.
36.	Zhang K, Xu Q, Gao Y, et al. Polysaccharides from Dicliptera chinensis ameliorate liver disturbance by regulating TLR-4/NF-κB and AMPK/Nrf2 signalling pathways. J Cell Mol Med, 2020, 24(11): 6397-6409.
37.	Brown AK, Webb AE. Regulation of FOXO factors in mammalian cells. Curr Top Dev Biol, 2018, 127: 165-192.
38.	Li Y, Chen Y. AMPK and autophagy. Adv Exp Med Biol, 2019, 1206: 85-108.
39.	Wang MJ, Tang WB, Zhu YZ. An update on AMPK in hydrogen sulfide pharmacology. Front Pharmacol, 2017, 8: 810.
40.	Yang F, Zhang L, Gao Z, et al. Exogenous H2S protects against diabetic cardiomyopathy by activating autophagy via the AMPK/mTOR pathway. Cell Physiol Biochem, 2017, 43(3): 1168-1187.
41.	Wang HG, Zhong PY, Sun LL. Exogenous hydrogen sulfide mitigates NLRP3 inflammasome-mediated inflammation through promoting autophagy via the AMPK-mTOR pathway. Biol Open, 2019, 8(7): bio043653.

1. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA, 2016, 315(8): 801-810.
2. Xie J, Wang H, Kang Y, et al. The epidemiology of sepsis in Chinese ICUs: A national cross-sectional survey. Crit Care Med, 2020, 48(3): e209-e218.
3. Huang M, Cai SL, Su JQ. The pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci, 2019, 20(21): 5376.
4. Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Crit Care Med, 2018, 46(6): 997-1000.
5. Feng Y, Liu B, Zheng X, et al. The protective role of autophagy in sepsis. Microb Pathog, 2019, 131: 106-111.
6. Yin X, Xin H, Mao S, et al. The role of autophagy in sepsis: protection and injury to organs. Front Physiol, 2019, 10: 1071.
7. Chen Y, Jin S, Teng X, et al. Hydrogen sulfide attenuates LPS-induced acute kidney injury by inhibiting inflammation and oxidative stress. Oxid Med Cell Longev, 2018, 2018: 6717212.
8. Jiang L, Jiang Q, Yang S, et al. GYY4137 attenuates LPS-induced acute lung injury via heme oxygenase-1 modulation. Pulm Pharmacol Ther, 2019, 54: 77-86.
9. Wu D, Wang H, Teng T, et al. Hydrogen sulfide and autophagy: A double edged sword. Pharmacol Res, 2018, 131: 120-127.
10. Qiu P, Liu Y, Zhang J. Review: the role and mechanisms of macrophage autophagy in sepsis. Inflammation, 2019, 42(1): 6-19.
11. Watanabe E, Thampy LK, Hotchkiss RS. Immunoadjuvant therapy in sepsis: novel strategies for immunosuppressive sepsis coming down the pike. Acute Med Surg, 2018, 5(4): 309-315.
12. Hsu C. Autophagy: A potential target for rescuing sepsis-induced hepatic failure. Chin J Physiol, 2019, 62(2): 53-62.
13. Li Y, Wang F, Luo Y. Ginsenoside Rg1 protects against sepsis-associated encephalopathy through beclin 1-independent autophagy in mice. J Surg Res, 2017, 207: 181-189.
14. Zhao Y, Feng X, Li B, et al. Dexmedetomidine protects against lipopolysaccharide-induced acute kidney injury by enhancing autophagy through inhibition of the PI3K/AKT/mTOR pathway. Front Pharmacol, 2020, 11: 128.
15. Yuan X, Chen G, Guo D, et al. Polydatin alleviates septic myocardial injury by promoting SIRT6-mediated autophagy. Inflammation, 2020, 43(3): 785-795.
16. Hu J, Shi Y, Wang C, et al. Role of intestinal trefoil factor in protecting intestinal epithelial cells from burn-induced injury. Sci Rep, 2018, 8(1): 3201.
17. Park SY, Shrestha S, Youn YJ, et al. Autophagy primes neutrophils for neutrophil extracellular trap formation during sepsis. Am J Respir Crit Care Med, 2017, 196(5): 577-589.
18. Shao Y, Chen F, Chen Y, et al. Association between genetic polymorphisms in the autophagy-related 5 gene promoter and the risk of sepsis. Sci Rep, 2017, 7(1): 9399.
19. Huang YY, Zhou F, Shen C, et al. LBP reduces the inflammatory injuryof kidney in septic rat and regulates the Keap1-Nrf2∕ARE signaling pathway1. Acta Cir Bras, 2019, 34(1): e20190010000003.
20. Ahmed SM, Luo L, Namani A, et al. Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis, 2017, 1863(2): 585-597.
21. Wen Z, Liu W, Li X, et al. A protective role of the NRF2-Keap1 pathway in maintaining intestinal barrier function. Oxid Med Cell Longev, 2019, 2019: 1759149.
22. Liao W, Wang Z, Fu Z, et al. p62/SQSTM1 protects against cisplatin-induced oxidative stress in kidneys by mediating the cross talk between autophagy and the Keap1-Nrf2 signalling pathway. Free Radic Res, 2019, 53(7): 800-814.
23. Zhao S, Song T, Gu Y, et al. Hydrogen sulfide alleviates liver injury via S-sulfhydrated-Keap1/Nrf2/LRP1 pathway. Hepatology, 2020: [Online ahead of print.
24. Wu JC, Tian ZL, Sun Y, et al. Exogenous H2S facilitating ubiquitin aggregates clearance via autophagy attenuates type 2 diabetes-induced cardiomyopathy. Cell Death Dis, 2017, 8(8): e2992.
25. Xiao Z, Liu L, Tao W, et al. Clostridium tyrobutyricum protect intestinal barrier function from LPS-induced apoptosis via P38/JNK signaling pathway in IPEC-J2 cells. Cell Physiol Biochem, 2018, 46(5): 1779-1792.
26. Dong N, Xu X, Xue C, et al. Ethyl pyruvate inhibits LPS induced IPEC-J2 inflammation and apoptosis through p38 and ERK1/2 pathways. Cell Cycle, 2019, 18(20): 2614-2628.
27. Zhu W, Lu Q, Wan L, et al. Sodium tanshinone ⅡA sulfonate ameliorates microcirculatory disturbance of small intestine by attenuating the production of reactie oxygen species in rats with sepsis. Chin J Integr Med, 2016, 22(10): 745-751.
28. Zhou M, Xu W, Wang J, et al. Boosting mTOR-dependent autophagy via upstream TLR4-MyD88-MAPK signalling and downstream NF-κB pathway quenches intestinal inflammation and oxidative stress injury. EBioMedicine, 2018, 35: 345-360.
29. He Y, She H, Zhang T, et al. p38 MAPK inhibits autophagy and promotes microglial inflammatory responses by phosphorylating ULK1. J Cell Biol, 2018, 217(1): 315-328.
30. Schwartz M, Böckmann S, Borchert P, et al. SB202190 inhibits endothelial cell apoptosis via induction of autophagy and heme oxygenase-1. Oncotarget, 2018, 9(33): 23149-23163.
31. Zhang GY, Lu D, Duan SF, et al. Hydrogen sulfide alleviates lipopolysaccharide-induced diaphragm dysfunction in rats by reducing apoptosis and inflammation through ROS/MAPK and TLR4/NF-kappaB signaling pathways. Oxid Med Cell Longev, 2018, 2018: 9647809.
32. Han X, Mao Z, Wang S, et al. GYY4137 protects against MCAO via p38 MAPK mediated anti-apoptotic signaling pathways in rats. Brain Res Bull, 2020, 158: 59-65.
33. Zhu MJ, Sun X, Du M. AMPK in regulation of apical junctions and barrier function of intestinal epithelium. Tissue Barriers, 2018, 6(2): 1-13.
34. Kitzmiller L, Ledford JR, Hake PW, et al. Activation of AMP-activated protein kinase by A769662 ameliorates sepsis-induced acute lung injury in adult mice. Shock, 2019, 52(5): 540-549.
35. Shimizu Y, Polavarapu R, Eskla KL, et al. Hydrogen sulfide regulates cardiac mitochondrial biogenesis via the activation of AMPK. J Mol Cell Cardiol, 2018, 116: 29-40.
36. Zhang K, Xu Q, Gao Y, et al. Polysaccharides from Dicliptera chinensis ameliorate liver disturbance by regulating TLR-4/NF-κB and AMPK/Nrf2 signalling pathways. J Cell Mol Med, 2020, 24(11): 6397-6409.
37. Brown AK, Webb AE. Regulation of FOXO factors in mammalian cells. Curr Top Dev Biol, 2018, 127: 165-192.
38. Li Y, Chen Y. AMPK and autophagy. Adv Exp Med Biol, 2019, 1206: 85-108.
39. Wang MJ, Tang WB, Zhu YZ. An update on AMPK in hydrogen sulfide pharmacology. Front Pharmacol, 2017, 8: 810.
40. Yang F, Zhang L, Gao Z, et al. Exogenous H2S protects against diabetic cardiomyopathy by activating autophagy via the AMPK/mTOR pathway. Cell Physiol Biochem, 2017, 43(3): 1168-1187.
41. Wang HG, Zhong PY, Sun LL. Exogenous hydrogen sulfide mitigates NLRP3 inflammasome-mediated inflammation through promoting autophagy via the AMPK-mTOR pathway. Biol Open, 2019, 8(7): bio043653.

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Research on mechanism of hydrogen sulfide in regulating autophagy to protect organ dysfunction in sepsis

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