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명태(Theragra chalcogramma) 껍질 유래 젤라틴 가수분해물의 항 HIV-1 효능

Anti-HIV-1 Activity of Gelatin Hydrolysate Derived from Alaska Pollack Theragra chalcogramma Skin

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초록

Infection with HIV [Human immunodeficiency virus], over time, develops into acquired immunodeficiency syndrome (AIDS). The development of non-toxic and effective anti-HIV drugs is one of the most promising strategies for the treatment of AIDS. In this study, we investigated the anti-HIV-1 activity of gelatin hydrolysates from Alaska pollack skin. Gelatin hydrolysates were prepared using four enzymes (alcalase, flavourzyme, neutrase, and pronase E). Among these, the pronase E gelatin hydrolysate was found to inhibit HIV-1 infection in the human T cell-line MT4. It exhibited inhibitory activity on HIV-1IIIB-induced cell lysis, reverse transcriptase activity, and viral p24 production at noncytotoxic concentrations. Moreover, it decreased the activation of matrix metalloproteinase-2 (MMP-2) in vitro. Because HIV infection-induced activation of MMP-2 can accelerate collagen resolution and collapse of the immune system, pronase E gelatin hydrolysate might prevent the activation of MMP-2 in cells, resulting in collagen stabilization and immune cell homeostasis consistent with anti-HIV activation. These results suggest that pronase E gelatin hydrolysate could potentially be incorporated into a novel therapeutic agent for HIV/AIDS patients.

Abstract

Infection with HIV [Human immunodeficiency virus], over time, develops into acquired immunodeficiency syndrome (AIDS). The development of non-toxic and effective anti-HIV drugs is one of the most promising strategies for the treatment of AIDS. In this study, we investigated the anti-HIV-1 activity of gelatin hydrolysates from Alaska pollack skin. Gelatin hydrolysates were prepared using four enzymes (alcalase, flavourzyme, neutrase, and pronase E). Among these, the pronase E gelatin hydrolysate was found to inhibit HIV-1 infection in the human T cell-line MT4. It exhibited inhibitory activity on HIV-1IIIB-induced cell lysis, reverse transcriptase activity, and viral p24 production at noncytotoxic concentrations. Moreover, it decreased the activation of matrix metalloproteinase-2 (MMP-2) in vitro. Because HIV infection-induced activation of MMP-2 can accelerate collagen resolution and collapse of the immune system, pronase E gelatin hydrolysate might prevent the activation of MMP-2 in cells, resulting in collagen stabilization and immune cell homeostasis consistent with anti-HIV activation. These results suggest that pronase E gelatin hydrolysate could potentially be incorporated into a novel therapeutic agent for HIV/AIDS patients.

참고문헌 (14)

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  2. F Barre-Sinoussi, "Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS)", Science, 220(4599), pp.868~871 (1983), American Association for the Advancement of Science (AAAS)[DOI]
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  4. Alba Diaz, "Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients", AIDS, 24(13), pp.2029~2039 (2010), Ovid Technologies (Wolters Kluwer Health)[DOI]
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  6. R. Gallo, "Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS)", Science, 220(4599), pp.865~867 (1983), American Association for the Advancement of Science (AAAS)[DOI]
  7. 허민수, "명태 수리미 부산물 유래 젤라틴 가수분해물을 이용한 시판 간장의 항산화성 및 ACE 저해활성의 개선", 한국수산과학회지, 43(3), pp.179~187 (2010), 한국수산과학회
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  11. Alberto Plaza, "Celebesides A−C and Theopapuamides B−D, Depsipeptides from an Indonesian Sponge That Inhibit HIV-1 Entry", The Journal of Organic Chemistry, 74(2), pp.504~512 (2009), American Chemical Society (ACS)[DOI]
  12. Martin Ruehl, "Hydroxyproline-containing collagen analogs trigger the release and activation of collagen-sequestered proMMP-2 by competition with prodomain-derived peptide P33-42", Fibrogenesis & Tissue Repair, 4(1), pp.33~42 (2011), Springer Nature[DOI]
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