Changes in blood carnitine and acylcarnitine profiles of very long-chain acyl-CoA dehydrogenase-deficient mice subjected to stress
Changes in blood carnitine and acylcarnitine profiles of very long-chain acyl-CoA dehydrogenase-deficient mice subjected to stress
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DOI：
10.1111/j.1365-2362.2004.01308.x
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发表时间：
2004-03-01
影响因子：
5.5
通讯作者：
Strauss, AW
中科院分区：
文献类型：
--
作者：
Spiekerkoetter, U;Tokunaga, C;Strauss, AW
在缺乏极长链酰基辅酶A脱氢酶（VLCAD）的人类中，C14-C18酰基肉毒碱积累。在本文中，我们已经使用VLCAD基因敲除小鼠作为模型，以研究血液中的肉毒碱和酰基肉毒碱的变化概况下stress.Design VLCAD基因敲除小鼠表现出应激诱导的低血糖和骨骼肌病变，类似于人类VLCADD的症状。为了研究生化紊乱的程度，在不同的压力，我们确定了血液中的肉毒碱和acylcarnitine配置文件后，在跑步机上运动，禁食，或暴露于cold.Results即使在一个nonstressed，良好的喂养状态，基因敲除小鼠提出了两倍高的C14-C18 acylcarnitines和较低的游离肉毒碱的72%相比，野生型同窝。剧烈运动1 h后，血中C14-C18酰基肉毒碱含量显著增加，而游离肉毒碱含量无明显变化。在4 ℃禁食8小时后，与未应激的野生型小鼠相比，敲除小鼠中的长链酰基肉毒碱浓度升高了5倍（P < 0.05），12只敲除小鼠中有4只死亡。与未应激的野生型小鼠相比，游离肉毒碱下降至44%。C14-C18酰基肉毒碱的增加和减少游离肉毒碱也观察到在禁食的杂合子和wild-type mice.Conclusions长链酰基肉毒碱在血液中的基因敲除小鼠在不同的应激源和浓度的增加与临床条件。在基因敲除小鼠和野生型同窝小鼠中观察到，严重应激后血液中游离肉毒碱的减少。监测血液中的酰基肉毒碱谱响应于不同的应激源，可以允许在VLCAD基因敲除小鼠的治疗干预的系统分析。
Background In humans with deficiency of the very long-chain acyl-CoA dehydrogenase (VLCAD), C14-C18 acylcarnitines accumulate. In this paper we have used the VLCAD knockout mouse as a model to study changes in blood carnitine and acylcarnitine profiles under stress.Design VLCAD knockout mice exhibit stress-induced hypoglycaemia and skeletal myopathy; symptoms resembling human VLCADD. To study the extent of biochemical derangement in response to different stressors, we determined blood carnitine and acylcarnitine profiles after exercise on a treadmill, fasting, or exposure to cold.Results Even in a nonstressed, well-fed state, knockout mice presented twofold higher C14-C18 acylcarnitines and a lower free carnitine of 72% as compared to wild-type littermates. After 1 h of intense exercise, the C14-C18 acylcarnitines in blood significantly increased, but free carnitine remained unchanged. After 8 h of fasting at 4 degreesC, the long-chain acylcarnitines were elevated 5-fold in knockout mice in comparison with concentrations in unstressed wild-type mice (P < 0.05), and four out of 12 knockout mice died. Free carnitine decreased to 44% as compared with unstressed wild-type mice. An increase in C14-C18 acylcarnitines and a decrease of free carnitine were also observed in fasted heterozygous and wild-type mice.Conclusions Long-chain acylcarnitines in blood increase in knockout mice in response to different stressors and concentrations correlate with the clinical condition. A decrease in blood free carnitine in response to severe stress is observed in knockout mice but also in wild-type littermates. Monitoring blood acylcarnitine profiles in response to different stressors may allow systematic analysis of therapeutic interventions in VLCAD knockout mice.