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CPT2 K79 acetylation regulates platelet life span
The short life span of platelets is a major challenge to platelet transfusion services because of the lack of effective intervention. Here, we found that the accumulation of long-chain acylcarnitines (LCACs) is responsible for mitochondrial damage and platelet storage lesion. Further studies showed...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Hematology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631617/ https://www.ncbi.nlm.nih.gov/pubmed/35728063 http://dx.doi.org/10.1182/bloodadvances.2021006687 |
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author | Fan, Xuemei Wang, Yang Cai, Xiaohong Shen, Yingzhi Xu, Tongran Xu, Yanyan Cheng, Jinke Wang, Xuefeng Zhang, Lin Dai, Jing Lin, Shuhai Liu, Junling |
author_facet | Fan, Xuemei Wang, Yang Cai, Xiaohong Shen, Yingzhi Xu, Tongran Xu, Yanyan Cheng, Jinke Wang, Xuefeng Zhang, Lin Dai, Jing Lin, Shuhai Liu, Junling |
author_sort | Fan, Xuemei |
collection | PubMed |
description | The short life span of platelets is a major challenge to platelet transfusion services because of the lack of effective intervention. Here, we found that the accumulation of long-chain acylcarnitines (LCACs) is responsible for mitochondrial damage and platelet storage lesion. Further studies showed that the blockade of fatty acid oxidation and the activation of AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase/carnitine palmitoyltransferase 1 (CPT1) pathways that promote fatty acid metabolism are important reasons for the accumulation of LCACs. The excessive accumulation of LCACs can cause mitochondrial damage and a short life span of stored platelets. The mechanism study elucidated that NAD(+) exhaustion and the subsequent decrease in sirtuin 3 (Sirt3) activity caused an increase in the level of CPT2 K79 acetylation, which is the primary cause of the blockade of fatty acid oxidation and the accumulation of LCACs. Blocking LCAC generation with the inhibitors of AMPK or CPT1, the agonists of Sirt3, and antioxidants tremendously retarded platelet storage lesion in vitro and prolonged the survival of stored platelets in vivo posttransfusion with single or combined use. In summary, we discovered that CPT2 acetylation attenuates fatty acid oxidation and exacerbates platelet storage lesion and may serve as a new target for improving platelet storage quality. |
format | Online Article Text |
id | pubmed-9631617 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-96316172022-11-04 CPT2 K79 acetylation regulates platelet life span Fan, Xuemei Wang, Yang Cai, Xiaohong Shen, Yingzhi Xu, Tongran Xu, Yanyan Cheng, Jinke Wang, Xuefeng Zhang, Lin Dai, Jing Lin, Shuhai Liu, Junling Blood Adv Platelets and Thrombopoiesis The short life span of platelets is a major challenge to platelet transfusion services because of the lack of effective intervention. Here, we found that the accumulation of long-chain acylcarnitines (LCACs) is responsible for mitochondrial damage and platelet storage lesion. Further studies showed that the blockade of fatty acid oxidation and the activation of AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase/carnitine palmitoyltransferase 1 (CPT1) pathways that promote fatty acid metabolism are important reasons for the accumulation of LCACs. The excessive accumulation of LCACs can cause mitochondrial damage and a short life span of stored platelets. The mechanism study elucidated that NAD(+) exhaustion and the subsequent decrease in sirtuin 3 (Sirt3) activity caused an increase in the level of CPT2 K79 acetylation, which is the primary cause of the blockade of fatty acid oxidation and the accumulation of LCACs. Blocking LCAC generation with the inhibitors of AMPK or CPT1, the agonists of Sirt3, and antioxidants tremendously retarded platelet storage lesion in vitro and prolonged the survival of stored platelets in vivo posttransfusion with single or combined use. In summary, we discovered that CPT2 acetylation attenuates fatty acid oxidation and exacerbates platelet storage lesion and may serve as a new target for improving platelet storage quality. American Society of Hematology 2022-08-26 /pmc/articles/PMC9631617/ /pubmed/35728063 http://dx.doi.org/10.1182/bloodadvances.2021006687 Text en © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. |
spellingShingle | Platelets and Thrombopoiesis Fan, Xuemei Wang, Yang Cai, Xiaohong Shen, Yingzhi Xu, Tongran Xu, Yanyan Cheng, Jinke Wang, Xuefeng Zhang, Lin Dai, Jing Lin, Shuhai Liu, Junling CPT2 K79 acetylation regulates platelet life span |
title | CPT2 K79 acetylation regulates platelet life span |
title_full | CPT2 K79 acetylation regulates platelet life span |
title_fullStr | CPT2 K79 acetylation regulates platelet life span |
title_full_unstemmed | CPT2 K79 acetylation regulates platelet life span |
title_short | CPT2 K79 acetylation regulates platelet life span |
title_sort | cpt2 k79 acetylation regulates platelet life span |
topic | Platelets and Thrombopoiesis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631617/ https://www.ncbi.nlm.nih.gov/pubmed/35728063 http://dx.doi.org/10.1182/bloodadvances.2021006687 |
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