Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damage
Acute kidney injury (AKI) is a complex and common set of multifactorial clinical syndromes, and associated with increased in-hospital mortality. There is increasing evidence that Hyperhomocysteinemia (HHcy) is highly associated with the development of a variety of kidney diseases, including AKI. How...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.967104/full |
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| author | Mei Zhang Rong Dong Jingjing Da Jingjing Da Jing Yuan Jing Yuan Yan Zha Yan Zha Yanjun Long Yanjun Long Yanjun Long |
| author_facet | Mei Zhang Rong Dong Jingjing Da Jingjing Da Jing Yuan Jing Yuan Yan Zha Yan Zha Yanjun Long Yanjun Long Yanjun Long |
| author_sort | Mei Zhang |
| collection | DOAJ |
| description | Acute kidney injury (AKI) is a complex and common set of multifactorial clinical syndromes, and associated with increased in-hospital mortality. There is increasing evidence that Hyperhomocysteinemia (HHcy) is highly associated with the development of a variety of kidney diseases, including AKI. However, the pathogenesis of HHcy in AKI remains unclear. In this study, we investigated the effect and mechanism of HHcy on cisplatin-induced AKI in mice and NRK-52E cells cultured with HHcy. We confirmed that mice with HHcy had higher serum levels of creatinine and more severe renal tubule injury after cisplatin injection. We found that HHcy aggravated renal mitochondrial damage, mainly manifested as decreased ATP β, significantly increased cytoplasmic Cyt C expression and the ADP/ATP ratio, and a significantly decreased mitochondrial DNA (mtDNA) copy number. In addition, we found that HHcy accelerated cisplatin-induced renal DNA damage; culturing NRK-52E cells with homocysteine (Hcy) could significantly increase apoptosis and mitochondrial damage. Interestingly, we found that Mdivi-1 reduced Hcy-induced mitochondrial damage, thereby reducing the level of apoptosis. In conclusion, these results suggest that HHcy might aggravate the development of AKI by increasing mitochondrial damage and that reducing Hcy levels or inhibiting mitochondrial damage may be a potential therapeutic strategy to delay the development of AKI. |
| first_indexed | 2024-04-12T13:59:29Z |
| format | Article |
| id | doaj.art-27ab3ef3a8e44728ae8774a415a7518a |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-12T13:59:29Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-27ab3ef3a8e44728ae8774a415a7518a2022-12-22T03:30:14ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-10-011310.3389/fphys.2022.967104967104Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damageMei Zhang0Rong Dong1Jingjing Da2Jingjing Da3Jing Yuan4Jing Yuan5Yan Zha6Yan Zha7Yanjun Long8Yanjun Long9Yanjun Long10Department of Nephrology, Guizhou Provincial Institute of Nephritic & Urinary Disease, Guizhou Provincial People’s Hospital, Guiyang, ChinaDepartment of Nephrology, Guizhou Provincial Institute of Nephritic & Urinary Disease, Guizhou Provincial People’s Hospital, Guiyang, ChinaDepartment of Nephrology, Guizhou Provincial Institute of Nephritic & Urinary Disease, Guizhou Provincial People’s Hospital, Guiyang, ChinaDepartment of Biomedicine, Guizhou University School of Medicine, Guizhou University, Guiyang, ChinaDepartment of Nephrology, Guizhou Provincial Institute of Nephritic & Urinary Disease, Guizhou Provincial People’s Hospital, Guiyang, ChinaDepartment of Biomedicine, Guizhou University School of Medicine, Guizhou University, Guiyang, ChinaDepartment of Nephrology, Guizhou Provincial Institute of Nephritic & Urinary Disease, Guizhou Provincial People’s Hospital, Guiyang, ChinaDepartment of Biomedicine, Guizhou University School of Medicine, Guizhou University, Guiyang, ChinaDepartment of Nephrology, Guizhou Provincial Institute of Nephritic & Urinary Disease, Guizhou Provincial People’s Hospital, Guiyang, ChinaDepartment of Biomedicine, Guizhou University School of Medicine, Guizhou University, Guiyang, ChinaDepartment of Nephrology, People’s Hospital of Zhenfeng County, Qianxinan, Guizhou, ChinaAcute kidney injury (AKI) is a complex and common set of multifactorial clinical syndromes, and associated with increased in-hospital mortality. There is increasing evidence that Hyperhomocysteinemia (HHcy) is highly associated with the development of a variety of kidney diseases, including AKI. However, the pathogenesis of HHcy in AKI remains unclear. In this study, we investigated the effect and mechanism of HHcy on cisplatin-induced AKI in mice and NRK-52E cells cultured with HHcy. We confirmed that mice with HHcy had higher serum levels of creatinine and more severe renal tubule injury after cisplatin injection. We found that HHcy aggravated renal mitochondrial damage, mainly manifested as decreased ATP β, significantly increased cytoplasmic Cyt C expression and the ADP/ATP ratio, and a significantly decreased mitochondrial DNA (mtDNA) copy number. In addition, we found that HHcy accelerated cisplatin-induced renal DNA damage; culturing NRK-52E cells with homocysteine (Hcy) could significantly increase apoptosis and mitochondrial damage. Interestingly, we found that Mdivi-1 reduced Hcy-induced mitochondrial damage, thereby reducing the level of apoptosis. In conclusion, these results suggest that HHcy might aggravate the development of AKI by increasing mitochondrial damage and that reducing Hcy levels or inhibiting mitochondrial damage may be a potential therapeutic strategy to delay the development of AKI.https://www.frontiersin.org/articles/10.3389/fphys.2022.967104/fullHyperhomocysteinemiaacute kidney injurymitochondrial damageDNA damageapoptosis |
| spellingShingle | Mei Zhang Rong Dong Jingjing Da Jingjing Da Jing Yuan Jing Yuan Yan Zha Yan Zha Yanjun Long Yanjun Long Yanjun Long Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damage Frontiers in Physiology Hyperhomocysteinemia acute kidney injury mitochondrial damage DNA damage apoptosis |
| title | Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damage |
| title_full | Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damage |
| title_fullStr | Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damage |
| title_full_unstemmed | Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damage |
| title_short | Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damage |
| title_sort | hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial damage |
| topic | Hyperhomocysteinemia acute kidney injury mitochondrial damage DNA damage apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.967104/full |
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