Graphene quantum dots induce cascadic apoptosis via interaction with proteins associated with anti-oxidation after endocytosis by Trypanosoma brucei
Trypanosoma brucei, the pathogen causing African sleeping sickness (trypanosomiasis) in humans, causes debilitating diseases in many regions of the world, but mainly in African countries with tropical and subtropical climates. Enormous efforts have been devoted to controlling trypanosomiasis, includ...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1022050/full |
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| author | Yiwei Xie Yiwei Xie Yiwei Xie Hongrui Liang Hongrui Liang Hongrui Liang Ning Jiang Ning Jiang Ning Jiang Dingyuan Liu Dingyuan Liu Dingyuan Liu Naiwen Zhang Naiwen Zhang Naiwen Zhang Qilong Li Qilong Li Qilong Li Kai Zhang Kai Zhang Kai Zhang Xiaoyu Sang Xiaoyu Sang Xiaoyu Sang Ying Feng Ying Feng Ying Feng Ran Chen Ran Chen Ran Chen Yiwei Zhang Yiwei Zhang Yiwei Zhang Qijun Chen Qijun Chen Qijun Chen |
| author_facet | Yiwei Xie Yiwei Xie Yiwei Xie Hongrui Liang Hongrui Liang Hongrui Liang Ning Jiang Ning Jiang Ning Jiang Dingyuan Liu Dingyuan Liu Dingyuan Liu Naiwen Zhang Naiwen Zhang Naiwen Zhang Qilong Li Qilong Li Qilong Li Kai Zhang Kai Zhang Kai Zhang Xiaoyu Sang Xiaoyu Sang Xiaoyu Sang Ying Feng Ying Feng Ying Feng Ran Chen Ran Chen Ran Chen Yiwei Zhang Yiwei Zhang Yiwei Zhang Qijun Chen Qijun Chen Qijun Chen |
| author_sort | Yiwei Xie |
| collection | DOAJ |
| description | Trypanosoma brucei, the pathogen causing African sleeping sickness (trypanosomiasis) in humans, causes debilitating diseases in many regions of the world, but mainly in African countries with tropical and subtropical climates. Enormous efforts have been devoted to controlling trypanosomiasis, including expanding vector control programs, searching for novel anti-trypanosomial agents, and developing vaccines, but with limited success. In this study, we systematically investigated the effect of graphene quantum dots (GQDs) on trypanosomal parasites and their underlying mechanisms. Ultrasmall-sized GQDs can be efficiently endocytosed by T. brucei and with no toxicity to mammalian-derived cells, triggering a cascade of apoptotic reactions, including mitochondrial disorder, intracellular reactive oxygen species (ROS) elevation, Ca2+ accumulation, DNA fragmentation, adenosine triphosphate (ATP) synthesis impairment, and cell cycle arrest. All of these were caused by the direct interaction between GQDs and the proteins associated with cell apoptosis and anti-oxidation responses, such as trypanothione reductase (TryR), a key protein in anti-oxidation. GQDs specifically inhibited the enzymatic activity of TryR, leading to a reduction in the antioxidant capacity and, ultimately, parasite apoptotic death. These data, for the first time, provide a basis for the exploration of GQDs in the development of anti-trypanosomials. |
| first_indexed | 2024-04-11T13:38:33Z |
| format | Article |
| id | doaj.art-4b31ef0b1f5c48e68b850d8872a5a596 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T13:38:33Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4b31ef0b1f5c48e68b850d8872a5a5962022-12-22T04:21:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10220501022050Graphene quantum dots induce cascadic apoptosis via interaction with proteins associated with anti-oxidation after endocytosis by Trypanosoma bruceiYiwei Xie0Yiwei Xie1Yiwei Xie2Hongrui Liang3Hongrui Liang4Hongrui Liang5Ning Jiang6Ning Jiang7Ning Jiang8Dingyuan Liu9Dingyuan Liu10Dingyuan Liu11Naiwen Zhang12Naiwen Zhang13Naiwen Zhang14Qilong Li15Qilong Li16Qilong Li17Kai Zhang18Kai Zhang19Kai Zhang20Xiaoyu Sang21Xiaoyu Sang22Xiaoyu Sang23Ying Feng24Ying Feng25Ying Feng26Ran Chen27Ran Chen28Ran Chen29Yiwei Zhang30Yiwei Zhang31Yiwei Zhang32Qijun Chen33Qijun Chen34Qijun Chen35Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Shenyang, ChinaResearch Unit for Pathogenic Mechanism of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Shenyang, ChinaResearch Unit for Pathogenic Mechanism of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Shenyang, ChinaResearch Unit for Pathogenic Mechanism of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Shenyang, ChinaResearch Unit for Pathogenic Mechanism of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Shenyang, ChinaResearch Unit for Pathogenic Mechanism of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Shenyang, ChinaResearch Unit for Pathogenic Mechanism of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Shenyang, ChinaResearch Unit for Pathogenic Mechanism of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Shenyang, ChinaResearch Unit for Pathogenic Mechanism of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Shenyang, ChinaResearch Unit for Pathogenic Mechanism of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Shenyang, ChinaResearch Unit for Pathogenic Mechanism of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Shenyang, ChinaResearch Unit for Pathogenic Mechanism of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, ChinaKey Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Shenyang, ChinaResearch Unit for Pathogenic Mechanism of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang Agricultural University, Shenyang, ChinaTrypanosoma brucei, the pathogen causing African sleeping sickness (trypanosomiasis) in humans, causes debilitating diseases in many regions of the world, but mainly in African countries with tropical and subtropical climates. Enormous efforts have been devoted to controlling trypanosomiasis, including expanding vector control programs, searching for novel anti-trypanosomial agents, and developing vaccines, but with limited success. In this study, we systematically investigated the effect of graphene quantum dots (GQDs) on trypanosomal parasites and their underlying mechanisms. Ultrasmall-sized GQDs can be efficiently endocytosed by T. brucei and with no toxicity to mammalian-derived cells, triggering a cascade of apoptotic reactions, including mitochondrial disorder, intracellular reactive oxygen species (ROS) elevation, Ca2+ accumulation, DNA fragmentation, adenosine triphosphate (ATP) synthesis impairment, and cell cycle arrest. All of these were caused by the direct interaction between GQDs and the proteins associated with cell apoptosis and anti-oxidation responses, such as trypanothione reductase (TryR), a key protein in anti-oxidation. GQDs specifically inhibited the enzymatic activity of TryR, leading to a reduction in the antioxidant capacity and, ultimately, parasite apoptotic death. These data, for the first time, provide a basis for the exploration of GQDs in the development of anti-trypanosomials.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1022050/fullgraphene quantum dotsendocytosisapoptosistrypanothione reductaseanti-trypanosomialsTrypanosoma brucei |
| spellingShingle | Yiwei Xie Yiwei Xie Yiwei Xie Hongrui Liang Hongrui Liang Hongrui Liang Ning Jiang Ning Jiang Ning Jiang Dingyuan Liu Dingyuan Liu Dingyuan Liu Naiwen Zhang Naiwen Zhang Naiwen Zhang Qilong Li Qilong Li Qilong Li Kai Zhang Kai Zhang Kai Zhang Xiaoyu Sang Xiaoyu Sang Xiaoyu Sang Ying Feng Ying Feng Ying Feng Ran Chen Ran Chen Ran Chen Yiwei Zhang Yiwei Zhang Yiwei Zhang Qijun Chen Qijun Chen Qijun Chen Graphene quantum dots induce cascadic apoptosis via interaction with proteins associated with anti-oxidation after endocytosis by Trypanosoma brucei Frontiers in Immunology graphene quantum dots endocytosis apoptosis trypanothione reductase anti-trypanosomials Trypanosoma brucei |
| title | Graphene quantum dots induce cascadic apoptosis via interaction with proteins associated with anti-oxidation after endocytosis by Trypanosoma brucei |
| title_full | Graphene quantum dots induce cascadic apoptosis via interaction with proteins associated with anti-oxidation after endocytosis by Trypanosoma brucei |
| title_fullStr | Graphene quantum dots induce cascadic apoptosis via interaction with proteins associated with anti-oxidation after endocytosis by Trypanosoma brucei |
| title_full_unstemmed | Graphene quantum dots induce cascadic apoptosis via interaction with proteins associated with anti-oxidation after endocytosis by Trypanosoma brucei |
| title_short | Graphene quantum dots induce cascadic apoptosis via interaction with proteins associated with anti-oxidation after endocytosis by Trypanosoma brucei |
| title_sort | graphene quantum dots induce cascadic apoptosis via interaction with proteins associated with anti oxidation after endocytosis by trypanosoma brucei |
| topic | graphene quantum dots endocytosis apoptosis trypanothione reductase anti-trypanosomials Trypanosoma brucei |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1022050/full |
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