七种蛋白酶抑制剂对多房棘球蚴DNA损伤诱导样1蛋白活性的影响

doi:10.11843/j.issn.0366-6964.2024.05.045

Abstract

Abstract: As no effective treatment for alveolar echinococcosis (AE) is currently available, the therapeutic drugs are needed urgently. Early stage studies have shown that the protease inhibitors of HIV could also be anticancer and anti-parasitic. The purpose of this paper is to study the effect of the inhibitors (HIV PIs) on the activity of DNA damage inducible 1 protein of Echinococcus multilocularis (EmuDdi1). The recombinant vector pFastBac1-EmuDdi1 was constructed and expressed in Sf9 cell, and the soluble protein was successfully purified in P2 generations. Then the enzyme activity of Ddi1 protein was detected with the specific fluorescent substrates, and the inhibition rate of seven HIV PIs including saquinavir (SQV), ritonavir (RTV), amprenavir (APV), atazanavir (ATV), lopinavir(LPV), fosamprenavir (Fos), tipranavir (TPV) and darunavir (DRV) on Ddi1 protein activity was further examined. The results showed that Emu Ddi1had high affinity and activity, and saquinavir showed the highest inhibition rate at 67% to inhibit protease activity of EmuDdi1 with a IC₅₀ at 34. These results suggested that saquinavir is effcetive to inhibit the activity of Ddi1, and could be used to develop a potential targeting drug for AE.

Key words: protease inhibitors, Echinococcus multilocularis, DNA damage inducible 1 protein, enzyme activity, inhibition rate

CLC Number:

S852.734

ZHANG Shengying, LIU Zhongli, GUO Aijiang, WANG Shuai. The Effect of Seven Protease Inhibitors on Activity of DNA Damage Inducible 1 Protein in Echinococcus multilocularis[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(5): 2273-2280.

References

[1] CASULLI A, BARTH T F E, TAMAROZZI F. Echinococcus multilocularis[J]. Trends Parasitol, 2019, 35(9):738-739.
[2] LIU Z L, GUO X L, GUO A J, et al. HIV protease inhibitor nelfinavir is a potent drug candidate against echinococcosis by targeting Ddi1-like protein[J]. eBioMedicine, 2022, 82:104177.
[3] KUMAR S, SUGUNA K. Crystal structure of the retroviral protease-like domain of a protozoal DNA damage-inducible 1 protein[J]. FEBS OpenBio, 2018, 8(9):1379-1394.
[4] WOOLSEY I D, MILLER A L. Echinococcus granulosus sensu lato and Echinococcus multilocularis: a review[J]. Res Vet Sci, 2021, 135:517-522.
[5] MÓTYÁN J A, MICZI M, TÖZSÉR J. Dimer interface organization is a main determinant of intermonomeric interactions and correlates with evolutionary relationships of retroviral and retroviral-like Ddi1 and Ddi2 proteases[J]. Int J Mol Sci, 2020, 21(4):1352.
[6] NOWICKA U, ZHANG D N, WALKER O, et al. DNA-damage-inducible 1 protein (Ddi1) contains an uncharacteristic ubiquitin-like domain that binds ubiquitin[J]. Structure, 2015, 23(3):542-557.
[7] GANTT S, CASPER C, AMBINDER R F. Insights into the broad cellular effects of nelfinavir and the HIV protease inhibitors supporting their role in cancer treatment and prevention[J]. Curr Opin Oncol, 2013, 25(5):495-502.
[8] ASAITHAMBI K, BISWAS I, SUGUNA K. Structural and functional insights into the DNA damage-inducible protein 1 (Ddi1) from protozoa[J]. Curr Res Struct Biol, 2022, 4:175-191.
[9] XIANG T, DU L Y, PHAM P, et al. Nelfinavir, an HIV protease inhibitor, induces apoptosis and cell cycle arrest in human cervical cancer cells via the ROS-dependent mitochondrial pathway[J]. Cancer Lett, 2015, 364(1):79-88.
[10] YIP M C J, BODNAR N O, RAPOPORT T A. Ddi1 is a ubiquitin-dependent protease[J]. Proc Natl Acad Sci U S A, 2020, 117(14):7776-7781.
[11] ELU N, OSINALDE N, BEASKOETXEA J, et al. Detailed dissection of UBE3A-mediated DDI1 ubiquitination[J]. Front Physiol, 2019, 10:534.
[12] PERTEGUER M J, GÓMEZ-PUERTAS P, CAÑAVATE C, et al. Ddi1-like protein from Leishmania major is an active aspartyl proteinase[J]. Cell Stress Chaperones, 2013, 18(2):171-181.
[13] WHITE R E, POWELL D J, BERRY C. HIV proteinase inhibitors target the Ddi1-like protein of Leishmania parasites[J]. FASEB J, 2011, 25(5):1729-1736.
[14] DANAHER R J, WANG C M, ROLAND A T, et al. HIV protease inhibitors block oral epithelial cell DNA synthesis[J]. Arch Oral Biol, 2010, 55(2):95-100.
[15] MAXSON T, DEANE C D, MOLLOY E M, et al. HIV protease inhibitors block streptolysin S production[J]. ACS Chem Biol, 2015, 10(5):1217-1226.
[16] SCHWAKE C, BALDWIN M R, BACHOVCHIN W, et al. HIV protease inhibitors block parasite signal peptide peptidases and prevent growth of Babesia microti parasites in erythrocytes[J]. Biochem Biophys Res Commun, 2019, 517(1):125-131.
[17] HUDON S E, COFFINIER C, MICHAELIS S, et al. HIV-protease inhibitors block the enzymatic activity of purified Ste24p[J]. Biochem Biophys Res Commun, 2008, 374(2):365-368.
[18] REBELLO K M, ANDRADE-NETO V V, ZUMA A A, et al. Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism of Leishmania amazonensis promastigotes[J]. Parasitology, 2018, 145(10):1304-1310.
[19] BACIGALUPO I, PALLADINO C, LEONE P, et al. Inhibition of MMP-9 expression by ritonavir or saquinavir is associated with inactivation of the AKT/Fra-1 pathway in cervical intraepithelial neoplasia cells[J]. Oncol Lett, 2017, 13(5):2903-2908.
[20] BARILLARI G, IOVANE A, BACIGALUPO I, et al. Ritonavir or saquinavir impairs the invasion of cervical intraepithelial neoplasia cells via a reduction of MMP expression and activity[J]. AIDS, 2012, 26(8):909-919.
[21] WU X D, LI Y Z, PENG K S, et al. HIV protease inhibitors in gut barrier dysfunction and liver injury[J]. Curr Opin Pharmacol, 2014, 19:61-66.
[22] FALKENSAMMER B, PILZ G, BEKTIĆ J, et al. Absent reduction by HIV protease inhibitors of Candida albicans adhesion to endothelial cells[J]. Mycoses, 2007, 50(3):172-177.
[23] ABOU-EL-NAGA I F, EL KERDANY E D, MADY R F, et al. The effect of lopinavir/ritonavir and lopinavir/ritonavir loaded PLGA nanoparticles on experimental toxoplasmosis[J]. Parasitol Int, 2017, 66(6):735-747.
[24] ABT D, BESSE A, SEDLARIKOVA L, et al. Improving the efficacy of proteasome inhibitors in the treatment of renal cell carcinoma by combination with the human immunodeficiency virus (HIV)-protease inhibitors lopinavir or nelfinavir[J]. BJU Int, 2018, 121(4):600-609.
[25] GRANATO Q M, SOUSA S I, ROSA T L S A, et al. Aspartic peptidase of Phialophora verrucosa as target of HIV peptidase inhibitors:blockage of its enzymatic activity and interference with fungal growth and macrophage interaction[J]. J Enzyme Inhib Med Chem, 2020, 35(1):629-638.
[26] BONDE C G, GAWAD J, BHOLE R P, et al. Effective drug candidates against global pandemic of Novel Corona Virus (nCoV-2019): A probability check through computational approach for public health emergency[J]. Russ J Bioorg Chem, 2023, 49(3):689-695.
[27] GOULIELMAKI E, KAFOROU S, VENUGOPAL K, et al. Distinct effects of HIV protease inhibitors and ERAD inhibitors on zygote to ookinete transition of the malaria parasite[J]. Mol Biochem Parasitol, 2018, 220:10-14.
[28] SANGENITO L S, D’AVILA-LEVY C M, BRANQUINHA M H, et al. Nelfinavir and lopinavir impair Trypanosoma cruzi trypomastigote infection in mammalian host cells and show anti-amastigote activity[J]. Int J Antimicrob Agents, 2016, 48(6):703-711.
[29] RICHMOND S R, CARPER M J, LEI X Y, et al. HIV-protease inhibitors suppress skeletal muscle fatty acid oxidation by reducing CD36 and CPT1 fatty acid transporters[J]. Biochim Biophys Acta, 2010, 1801(5):559-566.
[30] SZOKA L, KARNA E, ANDRULEWICZ-BOTULINSKA E, et al. The mechanism for differential effect of nelfinavir and indinavir on collagen metabolism in human skin fibroblasts[J]. Exp Dermatol, 2019, 28(7):845-853.
[31] YAO K, WANG Z, PENG C, et al. HIV protease inhibitor saquinavir inhibits toll-like receptor 4 activation by targeting receptor dimerization[J]. Immunopharmacol Immunotoxicol, 2023, 45(6):754-760.

The Effect of Seven Protease Inhibitors on Activity of DNA Damage Inducible 1 Protein in Echinococcus multilocularis

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