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Excessive hydrogen sulfide causes lung and brain tissue damage by promoting PARP1/Bax and C9 and inhibiting LAMB1

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Abstract

Excessive hydrogen sulfide (H2S) causes serious damage to human organs and tissues. In this study, we aimed to explore the role and underlying mechanism of excessive H2S in brain and lung tissues. A H2S concentration of 100–800 pm promotes apoptosis and inflammation of brain and lung cells in ICR mice. Mechanistically, a H2S concentration of 100–800 pm upregulates PARP1 and Bax expression in a dose-dependent manner in vivo and in vitro, and functional gain-and-loss experiments verified that an excessive amount of H2S plays a pro-apoptotic role in HT22 and MML1 cells via regulation of PARP1 and Bax in vitro. By combining animal and cell experiments, we clarified that excess H2S promotes the inflammatory response of mouse brain and lung cells by promoting the expression of C9. In addition, the downregulation of LAMB1 by an excessive H2S concentration was confirmed using mass spectrometry and western blotting in vivo and in vitro. Combined with in vitro experiments, we found that an excessive H2S concentration promotes the expression of STAT1 and EGFR in HT22 and MML1 cells by inhibiting the expression of LAMB1. In summary, 100–800 pm H2S causes the brain and lung tissue damage in ICR mice, the underlying mechanisms include H2S induced apoptosis and inflammation of mouse brain and lung cells by upregulation of PARP1/Bax and C9, respectively, and H2S might induce fibrosis of mouse brain and lung cells by downregulation of LAMB1.

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References

  1. Miyazaki Y, Marutani E, Ikeda T, Ni X, Hanaoka K, Xian M, Ichinose F (2021) A sulfonyl azide-based sulfide scavenger rescues mice from lethal hydrogen sulfide intoxication. Toxicol Sci 183:393–403

    Article  CAS  PubMed  Google Scholar 

  2. Ng PC, Hendry-Hofer TB, Witeof AE, Brenner M, Mahon SB, Boss GR, Haouzi P, Bebarta VS (2019) Hydrogen sulfide toxicity: mechanism of action, clinical presentation, and countermeasure development. J Med Toxicol 15:287–294

    Article  PubMed  PubMed Central  Google Scholar 

  3. Salloum FN (2015) Hydrogen sulfide and cardioprotection–Mechanistic insights and clinical translatability. Pharmacol Ther 152:11–17

    Article  CAS  PubMed  Google Scholar 

  4. Yang N, Liu Y, Li T, Tuo Q (2020) Role of hydrogen sulfide in chronic diseases. DNA Cell Biol 39:187–196

    Article  CAS  PubMed  Google Scholar 

  5. Kumar M, Sandhir R (2018) Hydrogen sulfide in physiological and pathological mechanisms in brain. CNS Neurol Disord: Drug Targets 17:654–670

    Article  CAS  Google Scholar 

  6. Haouzi P, Sonobe T, Judenherc-Haouzi A (2020) Hydrogen sulfide intoxication induced brain injury and methylene blue. Neurobiol Dis 133:104474

    Article  CAS  PubMed  Google Scholar 

  7. Tanaka S, Fujimoto S, Tamagaki Y, Wakayama K, Shimada K, Yoshikawa J (1999) Bronchial injury and pulmonary edema caused by hydrogen sulfide poisoning. Am J Emerg Med 17:427–429

    Article  CAS  PubMed  Google Scholar 

  8. Xiao Q, Ying J, Xiang L, Zhang C (2018) The biologic effect of hydrogen sulfide and its function in various diseases. Medicine 97:e13065

    Article  PubMed  PubMed Central  Google Scholar 

  9. Vida A, Marton J, Miko E, Bai P (2017) Metabolic roles of poly(ADP-ribose) polymerases. Semin Cell Dev Biol 63:135–143

    Article  CAS  PubMed  Google Scholar 

  10. Gallyas F Jr, Sumegi B (2020) Mitochondrial protection by PARP inhibition. Int J Mol Sci 21:2767

    Article  CAS  Google Scholar 

  11. Nikoletopoulou V, Markaki M, Palikaras K, Tavernarakis N (1833) Crosstalk between apoptosis, necrosis and autophagy. Biochem Biophys Acta 2013:3448–3459

    Google Scholar 

  12. R. Carpenter, M.F. Brady, BAX Gene, StatPearls, Treasure Island (FL), 2020.

  13. Zhu L, Yang B, Ma D, Wang L, Duan W (2020) Hydrogen Sulfide. Adipose Tissue and Diabetes Mellitus, Diabetes, metabolic syndrome and obesity : targets and therapy 13:1873–1886

    Google Scholar 

  14. F. Mollah, S. Tam, Complement Deficiency, StatPearls, Treasure Island (FL), 2020.

  15. Wang Y, Xing QQ, Tu JK, Tang WB, Yuan XN, Xie YY, Wang W, Peng ZZ, Huang L, Xu H, Qin J, Xiao XC, Tao LJ, Yuan QJ (2019) Involvement of hydrogen sulfide in the progression of renal fibrosis. Chin Med J 132:2872–2880

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chen W, Wu X, Yan X, Xu A, Yang A, You H (2019) Multitranscriptome analyses reveal prioritized genes specifically associated with liver fibrosis progression independent of etiology, American journal of physiology. Gastrointestinal Liver Physiol 316:G744–G754

    Article  CAS  Google Scholar 

  17. Ji X, Wu B, Han R, Yang J, Ayaaba E, Wang T, Han L, Ni C (2017) The association of LAMB1 polymorphism and expression changes with the risk of coal workers’ pneumoconiosis. Environ Toxicol 32:2182–2190

    Article  CAS  PubMed  Google Scholar 

  18. Bachman J (2013) Reverse-transcription PCR (RT-PCR). Methods Enzymol 530:67–74

    Article  CAS  PubMed  Google Scholar 

  19. Hnasko TS, Hnasko RM (2015) The western blot. Methods Mol Biol 1318:87–96

    Article  PubMed  Google Scholar 

  20. Kumar M, Ray RS, Sandhir R (2018) Hydrogen sulfide attenuates homocysteine-induced neurotoxicity by preventing mitochondrial dysfunctions and oxidative damage: In vitro and in vivo studies. Neurochem Int 120:87–98

    Article  CAS  PubMed  Google Scholar 

  21. Bhatia M (2015) H2S and inflammation: an overview. Handb Exp Pharmacol 230:165–180

    Article  CAS  PubMed  Google Scholar 

  22. Testai L, Brancaleone V, Flori L, Montanaro R, Calderone V (2021) Modulation of EndMT by hydrogen sulfide in the prevention of cardiovascular fibrosis. Antioxidants (Basel) 10:910

    Article  CAS  Google Scholar 

  23. Pan WJ, Fan WJ, Zhang C, Han D, Qu SL, Jiang ZS (2015) H2S, a novel therapeutic target in renal-associated diseases? Clinica Chimica Acta Int J Clin Chem 438:112–118

    Article  CAS  Google Scholar 

  24. Donnarumma E, Trivedi RK, Lefer DJ (2017) Protective actions of H2S in acute myocardial infarction and heart failure, comprehensive. Physiology 7:583–602

    Google Scholar 

  25. Shen Y, Shen Z, Luo S, Guo W, Zhu YZ (2015) The cardioprotective effects of hydrogen sulfide in heart diseases: from molecular mechanisms to therapeutic potential. Oxidative Med Cell Longevity 2015:925167

    Article  Google Scholar 

  26. Wu N, Du X, Wang D, Hao F (2011) Myocardial and lung injuries induced by hydrogen sulfide and the effectiveness of oxygen therapy in rats. Clin Toxicol 49:161–166

    Article  CAS  Google Scholar 

  27. Bliksoen M, Kaljusto ML, Vaage J, Stenslokken KO (2008) Effects of hydrogen sulphide on ischaemia-reperfusion injury and ischaemic preconditioning in the isolated, perfused rat heart. European J Cardio-thoracic Surg 34:344–349

    Article  Google Scholar 

  28. Hu Y, Chen X, Pan TT, Neo KL, Lee SW, Khin ES, Moore PK, Bian JS (2008) Cardioprotection induced by hydrogen sulfide preconditioning involves activation of ERK and PI3K/Akt pathways. Pflugers Arch 455:607–616

    Article  CAS  PubMed  Google Scholar 

  29. Wang H, Li X, Zhu Z, Wang H, Wei B, Bai X (2020) Hydrogen sulfide promotes lipopolysaccharide-induced apoptosis of osteoblasts by inhibiting the AKT/NF-kappaB signaling pathway. Biochem Biophys Res Commun 524:832–838

    Article  CAS  PubMed  Google Scholar 

  30. Wright RD, Dimou P, Northey SJ, Beresford MW (2019) Mesangial cells are key contributors to the fibrotic damage seen in the lupus nephritis glomerulus. J Inflamm 16:22

    Article  Google Scholar 

  31. Skibba M, Qian Y, Bao Y, Lan J, Peng K, Zhao Y, Zhong P, Hu J, Li X, Liang G (2016) New EGFR inhibitor, 453, prevents renal fibrosis in angiotensin II-stimulated mice. Eur J Pharmacol 789:421–430

    Article  CAS  PubMed  Google Scholar 

  32. Zhang M, Xin W, Yu Y, Yang X, Ma C, Zhang H, Liu Y, Zhao X, Guan X, Wang X, Zhu D (2020) Programmed death-ligand 1 triggers PASMCs pyroptosis and pulmonary vascular fibrosis in pulmonary hypertension. J Mol Cell Cardiol 138:23–33

    Article  CAS  PubMed  Google Scholar 

  33. Adinolfi M, Lehner T (1988) C9 and factor B as acute phase proteins and their diagnostic and prognostic value in disease. Exp Clin Immunogenet 5:123–132

    CAS  PubMed  Google Scholar 

  34. Wu M, Xu L, Wang Y, Zhou N, Zhen F, Zhang Y, Qu X, Fan H, Liu S, Chen Y, Yao R (2018) S100A8/A9 induces microglia activation and promotes the apoptosis of oligodendrocyte precursor cells by activating the NF-kappaB signaling pathway. Brain Res Bull 143:234–245

    Article  CAS  PubMed  Google Scholar 

  35. Shi Y, Guo X, Zhang J, Zhou H, Sun B, Feng J (2018) DNA binding protein HMGB1 secreted by activated microglia promotes the apoptosis of hippocampal neurons in diabetes complicated with OSA. Brain Behav Immun 73:482–492

    Article  CAS  PubMed  Google Scholar 

  36. Fann DY, Lim YA, Cheng YL, Lok KZ, Chunduri P, Baik SH, Drummond GR, Dheen ST, Sobey CG, Jo DG, Chen CL, Arumugam TV (2018) Evidence that NF-kappaB and MAPK signaling promotes NLRP inflammasome activation in neurons following ischemic stroke. Mol Neurobiol 55:1082–1096

    Article  CAS  PubMed  Google Scholar 

  37. Grynberg K, Ma FY, Nikolic-Paterson DJ (2017) The JNK signaling pathway in renal fibrosis. Front Physiol 8:829

    Article  PubMed  PubMed Central  Google Scholar 

  38. Yu T, Li YJ, Bian AH, Zuo HB, Zhu TW, Ji SX, Kong F, Yin DQ, Wang CB, Wang ZF, Wang HQ, Yang Y, Yoo BC, Cho JY (2014) The regulatory role of activating transcription factor 2 in inflammation. Mediators Inflam 2014:950472

    Article  Google Scholar 

  39. Li JK, Nie L, Zhao YP, Zhang YQ, Wang X, Wang SS, Liu Y, Zhao H, Cheng L (2016) IL-17 mediates inflammatory reactions via p38/c-Fos and JNK/c-Jun activation in an AP-1-dependent manner in human nucleus pulposus cells. J Transl Med 14:77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yan C, Deng C, Liu X, Chen Y, Ye J, Cai R, Shen Y, Tang H (2018) TNF-alpha induction of IL-6 in alveolar type II epithelial cells: Contributions of JNK/c-Jun/AP-1 element, C/EBPdelta/C/EBP binding site and IKK/NF-kappaB p65/kappaB site. Mol Immunol 101:585–596

    Article  CAS  PubMed  Google Scholar 

  41. Singh RK, Najmi AK, Dastidar SG (2017) Biological functions and role of mitogen-activated protein kinase activated protein kinase 2 (MK2) in inflammatory diseases. Pharmacological reports : PR 69:746–756

    Article  CAS  PubMed  Google Scholar 

  42. Singh RK, Najmi AK (2019) Novel therapeutic potential of mitogen-activated protein kinase activated Protein Kinase 2 (MK2) in chronic airway inflammatory disorders. Curr Drug Targets 20:367–379

    Article  CAS  PubMed  Google Scholar 

  43. Huang P, Han J, Hui L (2010) MAPK signaling in inflammation-associated cancer development. Protein Cell 1:218–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ou L, Lin S, Song B, Liu J, Lai R, Shao L (2017) The mechanisms of graphene-based materials-induced programmed cell death: a review of apoptosis, autophagy, and programmed necrosis. Int J Nanomed 12:6633–6646

    Article  CAS  Google Scholar 

  45. Dhanasekaran DN, Reddy EP (2017) JNK-signaling: A multiplexing hub in programmed cell death. Genes Cancer 8:682–694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by the Project of National Natural Science Foundation of China (81671868).

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    1. Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of Justice PRC, Shanghai, 200063, People’s Republic of China

      Ruxin Luo, Shaojie Zhuo, Xueyan Guo & Dong Ma

    2. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, People’s Republic of China

      Ting Wang

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    Luo, R., Wang, T., Zhuo, S. et al. Excessive hydrogen sulfide causes lung and brain tissue damage by promoting PARP1/Bax and C9 and inhibiting LAMB1. Apoptosis 27, 149–160 (2022). https://doi.org/10.1007/s10495-021-01705-w

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