CPT2 K79 acetylation regulates platelet life span.
CPT2 K79 acetylation regulates platelet life span.
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CPT2 K79 乙酰化调节血小板寿命
DOI：
10.1182/bloodadvances.2021006687
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发表时间：
2022-09-13
期刊：
影响因子：
7.5
通讯作者：
Liu, Junling
中科院分区：
文献类型：
--
作者：
Fan, Xuemei;Wang, Yang;Cai, Xiaohong;Shen, Yingzhi;Xu, Tongran;Xu, Yanyan;Cheng, Jinke;Wang, Xuefeng;Zhang, Lin;Dai, Jing;Lin, Shuhai;Liu, Junling
NAD+耗竭和SIRT3功能障碍导致CPT2 K79乙酰化，导致LCAC积聚和血小板损伤。用AMPK或CPT1抑制剂、SIRT3激动剂和抗氧化剂阻断酰卡尼汀的产生可延缓血小板储存损伤。由于缺乏有效的干预措施，血小板寿命短是对血小板输注服务的一大挑战。在这里，我们发现长链酰肉碱(LCACs)的积聚是线粒体损伤和血小板储存损伤的原因。进一步的研究表明，抑制脂肪酸氧化和激活AMP激活的蛋白激酶(AMPK)/乙酰辅酶A羧基酶/肉碱棕榈酰转移酶1(CPT1)途径促进脂肪酸代谢是LCACs积累的重要原因。LCACs的过度积聚会导致线粒体损伤和储存的血小板寿命缩短。机制研究表明，NAD+的耗竭和sirtuin3(SIRT3)活性的降低导致CPT2 K79乙酰化水平的增加，这是阻止脂肪酸氧化和LCACs积累的主要原因。用AMPK或CPT1抑制剂、SIRT3激动剂和抗氧化剂阻断LCAC的生成，可显著延缓体外保存的血小板损伤，延长体内保存的血小板单独或联合使用后的存活时间。综上所述，我们发现CPT2乙酰化可减轻脂肪酸氧化和加重血小板储存损伤，并可能成为改善血小板储存质量的新靶点。
CPT2 K79 acetylation caused by NAD+ exhaustion and Sirt3 dysfunction resulted in LCAC accumulation and platelet damage. Blocking acylcarnitine generation with AMPK or CPT1 inhibitors, Sirt3 agonists, and antioxidants retarded platelet storage lesion. 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.
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影响因子：
64.5
作者：
Mason, Kylie D.;Carpinelli, Marina R.;Kile, Benjamin T.
通讯作者：
Kile, Benjamin T.
DOI：
10.1152/ajpendo.00602.2014
发表时间：
2015-06-01
影响因子：
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作者：
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作者：
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通讯作者：
Palankar, Raghavendra