Increase of reduced nicotinamide adenine dinucleotide fluorescence lifetime precedes mitochondrial dysfunction in staurosporine-induced apoptosis of HeLa cells.
Increase of reduced nicotinamide adenine dinucleotide fluorescence lifetime precedes mitochondrial dysfunction in staurosporine-induced apoptosis of HeLa cells.
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DOI：
10.1117/1.3560513
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发表时间：
2011-03
影响因子：
3.5
通讯作者：
Jia-Sin Yu;H. Guo;Chih-Hao Wang;Yau-Huei Wei;Hsing-Wen Wang
中科院分区：
文献类型：
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作者：
Jia-Sin Yu;H. Guo;Chih-Hao Wang;Yau-Huei Wei;Hsing-Wen Wang
细胞凋亡的体内无创检测代表了一种新工具，可以产生更明确的诊断、更准确的预后，并有助于改善人类疾病的治疗。还原型烟酰胺腺嘌呤二核苷酸（NADH）的内在荧光可能是细胞凋亡检测的潜在光学生物标志物，因为NADH参与线粒体膜电位（ΔΨ）形成和腺苷-5'-三磷酸（ATP）合成的呼吸，而ΔΨ和ATP水平的消耗是细胞凋亡的标志。我们之前观察到 NADH 荧光寿命的变化与星形孢菌素 (STS) 诱导的线粒体介导的细胞凋亡有关。但其与ΔΨ、ATP、耗氧率等线粒体功能的关系尚不清楚。在这项研究中，我们研究了这种关系。我们的结果表明，当 ΔΨ 和 ATP 水平等于或高于对照值时，NADH 荧光寿命增加；在 ΔΨ 和 ATP 耗尽之前，NADH 荧光寿命减少，而耗氧率没有变化。这些发现表明，STS 诱导的细胞死亡中 NADH 荧光寿命的增加发生在 ΔΨ 和 ATP 耗尽以及 caspase 3 激活之前，而不仅仅是由细胞代谢变化引起的。此外，NADH荧光寿命的变化与细胞凋亡的速度相关。
In vivo noninvasive detection of apoptosis represents a new tool that may yield a more definite diagnosis, a more accurate prognosis, and help improve therapies for human diseases. The intrinsic fluorescence of reduced nicotinamide adenine dinucleotide (NADH) may be a potential optical biomarker for the apoptosis detection because NADH is involved in the respiration for the mitochondrial membrane potential (ΔΨ) formation and adenosine-5'-triphosphate (ATP) synthesis, and the depletion of ΔΨ and ATP level is the hallmark of apoptosis. We have previously observed the NADH fluorescence lifetime change is associated with staurosporine (STS)-induced mitochondria-mediated apoptosis. However, its relationship with mitochondrial functions such as ΔΨ, ATP, and oxygen consumption rate is not clear. In this study, we investigated this relationship. Our results indicate that the NADH fluorescence lifetime increased when ΔΨ and ATP levels were equal to or higher than their values of controls and decreased before the depletion of ΔΨ and ATP, and the oxygen consumption rate did not change. These findings suggest that the increased NADH fluorescence lifetime in STS-induced cell death occurred before the depletion of ΔΨ and ATP and activation of caspase 3, and was not simply caused by cellular metabolic change. Furthermore, the NADH fluorescence lifetime change is associated with the pace of apoptosis.