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Article

Human trypsin inhibitor reduces the apoptosis of lipopolysaccharide‑induced human kidney‑2 cells by promoting mitochondrial fusion

  • Authors:
    • Ning Liu
    • Zhiyi Jiang
    • Yongjun Liu
    • Yao Nie
    • Juan Chen
    • Bin Ouyang
    • Xiangdong Guan
    • Minying Chen
  • View Affiliations / Copyright

    Affiliations: Department of Surgical Intensive Care Unit of The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China
  • Pages: 2899-2906
    |
    Published online on: July 5, 2017
       https://doi.org/10.3892/mmr.2017.6927
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Abstract

Imbalance in mitochondrial fusion/fission is one of the mechanisms leading to sepsis‑induced mitochondrial dysfunction and cell apoptosis. The present study examined the effects of human trypsin inhibitor (UTI), a well‑known antioxidant and anti‑inflammatory substance, on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)‑induced human kidney‑2 (HK‑2) cells. The HK‑2 cells were incubated for 24 h either with LPS (800 ng/ml) or LPS (800 ng/ml) mixed with UTI (250 U/ml). Cell viability was assessed using a3‑(4,5‑dimethyl‑2‑thiazolyl)‑2, 5‑diphenyl‑2‑H‑tetrazolium bromide assay. Oxidative activities (estimated by maleic dialdehyde and superoxide dismutase), levels of inflammatory cytokines interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α, and levels of ATP were measured using an enzyme‑linked immunosorbent assay. The expression levels of the mitochondrial fission protein, death‑associated protein kinase 2 (DAPK‑2), mitofusin (Mfn)1 and Mfn2 mitochondrial fusion proteins, and apoptotic and anti‑apoptotic biomarkers, including cytochrome c, caspase‑3, caspase‑9, B‑cell lymphoma (Bcl)‑2, Bcl‑extra large and poly ADP‑ribose polymerase (PARP), were assessed using western blot analyses. The changes in mitochondrial membrane potential were analyzed following JC‑1 staining. Annexin V/propidium iodide assays were used to evaluate cell apoptosis. The results showed that the balance of mitochondrial dynamics was towards mitochondrial fusion in the UTI group, as a reduced expression of DAPK2, and increased expression levels of Mfn1 and Mfn2 were detected (P<0.05, vs. LPS group). In addition, adecline in the levels of the inflammatory cytokines, TNF‑α and IL‑6, and the oxidative activities, reflected by an increase in SOD and a decrease in MDA (P<0.05, vs. LPS group) were observed. Cell apoptosis was inhibited following co‑treatment with UTI (P<0.05, vs. LPS group). It was concluded that UTI may protect mitochondrial functions by promoting mitochondrial fusion and limiting mitochondrial fission, thus reducing the apoptosis of LPS‑induced HK‑2 cells.
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View References

1 

Schrier RW and Wang W: Acute renal failure and sepsis. N Engl J Med. 351:159–169. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Russell JA: Management of sepsis. N Engl J Med. 355:1699–1713. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Gonzalez AS, Elguero ME, Finocchietto P, Holod S, Romorini L, Miriuka SG, Peralta JG, Poderoso JJ and Carreras MC: Abnormal mitochondrial fusion-fission balance contributes to the progression of experimental sepsis. Free Radic Res. 48:769–783. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Jendrach M, Mai S, Pohl S, Vöth M and Bereiter-Hahn J: Short- and long-term alterations of mitochondrial morphology, dynamics and mtDNA after transient oxidative stress. Mitochondrion. 8:293–304. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Binns OA, DeLima NF, Buchanan SA, Mauney MC, Cope JT, Thies SD, Shockey KS, Tribble CG and Kron IL: Neutrophil endopeptidase inhibitor improves pulmonary function during reperfusion after eighteen-hour preservation. J Thorac Cardiovasc Surg. 112:607–613. 1996. View Article : Google Scholar : PubMed/NCBI

6 

Hirose J, Ozawa T, Miura T, Isaji M, Nagao Y, Yamashiro K, Nii A, Kato K and Uemura A: Human neutrophil elastase degrades inter-alpha-trypsin inhibitor to liberate urinary trypsin inhibitor related proteins. Biol Pharm Bull. 21:651–656. 1998. View Article : Google Scholar : PubMed/NCBI

7 

Tanaka R, Fujita M, Tsuruta R, Fujimoto K, Aki HS, Kumagai K, Aoki T, Kobayashi A, Izumi T, Kasaoka S, et al: Urinary trypsin inhibitor suppresses excessive generation of superoxide anion radical, systemic inflammation, oxidative stress and endothelial injury in endotoxemic rats. Inflamm Res. 59:597–606. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Ueki M, Yokono S and Ogli K: Effects of ulinastation on rat renal energy metabolism and blood flow in hemorrhagic shock. J Anesth. 9:65–69. 1995. View Article : Google Scholar : PubMed/NCBI

9 

Taie S, Yokono S, Ueki M and Ogli K: Effects of ulinastatin (urinary trypsin inhibitor) on ATP, intracellular pH, andintracellular sodium transients during ischemia and reperfusion in the rat kidney in vivo. J Anesth. 15:33–38. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Ryan MJ, Johnson G, Kirk J, Fuerstenberg SM, Zager RA and Torok-Storb B: HK-2: An immortalized proximal tubule epithelial cell line from normal adult human kidney. Kidney Int. 45:48–57. 1994. View Article : Google Scholar : PubMed/NCBI

11 

Lerolle N, Nochy D, Guérot E, Bruneval P, Fagon JY, Diehl JL and Hill G: Histopathology of septic shock induced acute kidney injury: Apoptosis and leukocytic infiltration. Intensive Care Med. 36:471–478. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Jacobs R, Honore PM, Joannes-Boyau O, Boer W, De Regt J, De Waele E, Collin V and Spapen HD: Septic acute kidney injury: The culprit is inflammatory apoptosis rather than ischemic necrosis. Blood Purif. 32:262–265. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Koçkara A and Kayataş M: Renal cell apoptosis and new treatment options in sepsis-induced acute kidney injury. Ren Fail. 35:291–294. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Nunnari J, Wong ED, Meeusen S and Wagner JA: Studying the behavior of mitochondria. Methods Enzymol. 351:381–393. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Palmer CS, Osellame LD, Stojanovski D and Ryan MT: The regulation of mitochondrial morphology: Intricate mechanisms and dynamic machinery. Cell Signal. 23:1534–1545. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES and Wang X: Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 91:479–489. 1997. View Article : Google Scholar : PubMed/NCBI

17 

Tang WX, Wu WH, Qiu HY, Bo H and Huang SM: Amelioration of rhabdomyolysis-induced renal mitochondrial injury and apoptosis through suppression of Drp-1 translocation. J Nephrol. 26:1073–1082. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Zhang L, Jiang F, Chen Y, Luo J, Liu S, Zhang B, Ye Z, Wang W, Liang X and Shi W: Necrostatin-1 attenuates ischemia injury induced cell death in rat tubular cell line NRK-52E through decreased Drp1 expression. Int J Mol Sci. 14:24742–24754. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Gall JM, Wang Z, Liesa M, Molina A, Havasi A, Schwartz JH, Shirihai O, Borkan SC and Bonegio RG: Role of mitofusin 2 in the renal stress response. PLoS One. 7:e310742012. View Article : Google Scholar : PubMed/NCBI

20 

Ueki M, Taie S, Chujo K, Asaga T, Iwanaga Y, Ono J and Maekawa N: Urinary trypsin inhibitor reduces inflammatory response in kidney induced by lipopolysaccharide. J Biosci Bioeng. 104:315–320. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Wu S, Zhou F, Zhang Z and Xing D: Mitochondrial oxidative stress causes mitochondrial fragmentation via differential modulation of mitochondrial fission-fusion proteins. FEBS J. 278:941–954. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Motori E, Puyal J, Toni N, Ghanem A, Angeloni C, Malaguti M, Cantelli-Forti G, Berninger B, Conzelmann KK, Götz M, et al: Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance. Cell Metab. 18:844–859. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu N, Jiang Z, Liu Y, Nie Y, Chen J, Ouyang B, Guan X and Chen M: Human trypsin inhibitor reduces the apoptosis of lipopolysaccharide‑induced human kidney‑2 cells by promoting mitochondrial fusion. Mol Med Rep 16: 2899-2906, 2017.
APA
Liu, N., Jiang, Z., Liu, Y., Nie, Y., Chen, J., Ouyang, B. ... Chen, M. (2017). Human trypsin inhibitor reduces the apoptosis of lipopolysaccharide‑induced human kidney‑2 cells by promoting mitochondrial fusion. Molecular Medicine Reports, 16, 2899-2906. https://doi.org/10.3892/mmr.2017.6927
MLA
Liu, N., Jiang, Z., Liu, Y., Nie, Y., Chen, J., Ouyang, B., Guan, X., Chen, M."Human trypsin inhibitor reduces the apoptosis of lipopolysaccharide‑induced human kidney‑2 cells by promoting mitochondrial fusion". Molecular Medicine Reports 16.3 (2017): 2899-2906.
Chicago
Liu, N., Jiang, Z., Liu, Y., Nie, Y., Chen, J., Ouyang, B., Guan, X., Chen, M."Human trypsin inhibitor reduces the apoptosis of lipopolysaccharide‑induced human kidney‑2 cells by promoting mitochondrial fusion". Molecular Medicine Reports 16, no. 3 (2017): 2899-2906. https://doi.org/10.3892/mmr.2017.6927
Copy and paste a formatted citation
x
Spandidos Publications style
Liu N, Jiang Z, Liu Y, Nie Y, Chen J, Ouyang B, Guan X and Chen M: Human trypsin inhibitor reduces the apoptosis of lipopolysaccharide‑induced human kidney‑2 cells by promoting mitochondrial fusion. Mol Med Rep 16: 2899-2906, 2017.
APA
Liu, N., Jiang, Z., Liu, Y., Nie, Y., Chen, J., Ouyang, B. ... Chen, M. (2017). Human trypsin inhibitor reduces the apoptosis of lipopolysaccharide‑induced human kidney‑2 cells by promoting mitochondrial fusion. Molecular Medicine Reports, 16, 2899-2906. https://doi.org/10.3892/mmr.2017.6927
MLA
Liu, N., Jiang, Z., Liu, Y., Nie, Y., Chen, J., Ouyang, B., Guan, X., Chen, M."Human trypsin inhibitor reduces the apoptosis of lipopolysaccharide‑induced human kidney‑2 cells by promoting mitochondrial fusion". Molecular Medicine Reports 16.3 (2017): 2899-2906.
Chicago
Liu, N., Jiang, Z., Liu, Y., Nie, Y., Chen, J., Ouyang, B., Guan, X., Chen, M."Human trypsin inhibitor reduces the apoptosis of lipopolysaccharide‑induced human kidney‑2 cells by promoting mitochondrial fusion". Molecular Medicine Reports 16, no. 3 (2017): 2899-2906. https://doi.org/10.3892/mmr.2017.6927
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