【学术速递】辅酶I对缺氧心肌能量恢复过程具有重要作用
2015/8/3 平光制药辅酶I
缺血性心脏疾病会导致一系列严重威胁生命的并发症。常规治疗手段是增加冠状动脉灌注和抑制心肌收缩力、心率或血压，目的是增加氧供给和降低ATP消耗。辅助治疗手段是改善或优化心肌代谢。在缺血情况下心脏代谢抑制的特征是ATP和辅酶I(烟酰胺腺嘌呤二核苷酸，NAD+)含量降低。而缺血心脏中辅酶I(NAD+)的匮乏是由多个原因导致：1.还原型辅酶I(NADH)再生成辅酶I(NAD+)能力降低。2.氧化应激活化PARP导致辅酶I(NAD+)消耗增加。3.烟酰胺再合成辅酶I(NAD+)能力降低。最终导致细胞代谢受阻，细胞发生功能障碍。
德克萨斯大学医学部麻醉科Domokos Ger?等在最新一期《British journal of pharmacology》杂志发表了一项研究表明辅酶I(NAD+)再利用途径在缺氧后心肌细胞生物能量恢复中起着关键作用。研究发现在心肌氧糖剥夺损伤情况下，恢复辅酶I(NAD+)含量是ATP再生的先决条件并且观察到辅酶I(NAD+)代谢途径在生物能恢复中具有重要作用。该项研究发现：
1.缺氧后，能量池降低导致心肌细胞对氧化剂的敏感度增加。
2. 在心肌缺氧/复氧损伤情况下，辅酶I(NAD+)在ATP再生过程中具有重要作用。
3.辅酶I(NAD+)和ATP再生过程需要烟酰胺腺嘌呤磷酸核糖转移酶(NamPRT)介导的辅酶I(NAD+)再利用途径。
4.心肌缺氧后，辅酶I(NAD+)主要被PARP-1消耗，抑制PARP后会给缺血症状，甚至急性并发症带来益处。
原文摘要:
Nicotinamide adenine dinucleotide (NAD+ ) salvage plays critical rolein bioenergetic recovery of posthypoxic cardiomyocytes.
Ger? D1, Szabo C1.
BACKGROUND AND PURPOSE:
Ischemic heartdisease can lead to serious, life-threatening complications. Traditionaltherapies for ischemia aim to increase oxygen delivery and reduce themyocardial adenosine triphosphate (ATP) consumption by increasing the coronaryperfusion and by suppressing the cardiac contractility, heart rate or bloodpressure. An adjunctive treatment option for ischemia is to improve or optimizethe myocardial metabolism.
EXPERIMENTAL APPROACH:
Metabolicsuppression in the ischemic heart is characterized by reduced levels ofhigh-energy molecules: ATP and nicotinamide adenine dinucleotide (NAD+ ). SinceNAD+ is required for most metabolic processes that generate ATP, wehypothesized that restoration of NAD+ is a prerequisite for ATP regenerationand examined the role of the major NAD+ anabolic and catabolic pathways in thebioenergetic restoration following oxygen-glucose deprivation (OGD) injury incardiomyocytes.
KEY RESULTS:
We found that NAD+salvage via nicotinamide phosphoribosyl transferase (NamPRT) is essential forbioenergetic recovery in cardiomyocytes. Blockage of NamPRT prevents therestoration of the cellular ATP pool following oxygen-glucose deprivation (OGD)injury by inhibiting both the aerobic and anaerobic metabolism in the cells.NAD+ consumption by poly(ADP-ribose) polymerase-1 (PARP-1) also undermines therecovery processes and PARP inhibition significantly improves the metabolismand increases the cellular ATP level in cardiomyocytes.
CONCLUSIONS AND IMPLICATIONS:
We conclude thatthe NAD+ salvage pathway is requisite for bioenergetic recovery in posthypoxiccells and PARP inhibition may represent a potential future therapeuticintervention in ischemic heart disease.
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原文出处：
http://www.ncbi.nlm.nih.gov/pubmed/26218637?dopt=Abstract
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