Retinal flavoprotein fluorescence correlates with mitochondrial stress, apoptosis, and chemokine expression.
Retinal flavoprotein fluorescence correlates with mitochondrial stress, apoptosis, and chemokine expression.
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DOI：
10.1016/j.exer.2011.06.023
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发表时间：
2011-10
影响因子：
3.4
通讯作者：
Elner, Victor M.
中科院分区：
文献类型：
--
作者：
Field, Matthew G.;Yang, Dongli;Bian, Zong-Mei;Petty, Howard R.;Elner, Victor M.
关键词：
在许多视网膜疾病中，氧化应激和线粒体功能障碍发生在细胞凋亡之前。在这些条件下，更大部分的黄素蛋白被氧化，并且当被蓝光激发时，发射绿色黄素蛋白荧光（FPF）。在这项研究中，我们评估了FPF作为线粒体应激、凋亡前细胞不稳定性和细胞凋亡的早期指标的效用，这些指标包括体外过氧化氢（H2 O2）处理的人视网膜色素上皮（HRPE）细胞或单核细胞（未刺激或干扰素-γ刺激）以及体外H2 O2处理的新鲜分离的人和大鼠神经视网膜碎片。H2 O2暴露后HRPE细胞FPF增加与线粒体膜电位降低（Δ μ m）和细胞凋亡增加相关，呈时间和剂量依赖性。与单核细胞共培养的HRPE细胞具有增加的FPF，其以时间依赖性方式与Δ m降低、细胞凋亡增加以及促炎性趋化因子、白细胞介素-8（IL-8）和单核细胞趋化因子-1（MCP-1）的早期表达相关，已知其由氧化应激诱导。早在暴露于应激物后1-2小时，FPF增加，Δ m降低，IL 8和MCP 1上调，而HRPE细胞中直到更晚的时间点才发生凋亡。抗氧化剂，N-乙酰半胱氨酸（NAC），抑制增加FPF和细胞凋亡的HRPE细胞受到过氧化氢。人和大鼠神经视网膜的FPF增加也与细胞凋亡增加相关。这项研究表明，FPF是视网膜细胞和组织中线粒体功能的一种有用的测量方法，可以检测可能先于细胞凋亡的早期线粒体功能障碍。
Oxidative stress and mitochondrial dysfunction occur before apoptosis in many retinal diseases. Under these conditions, a larger fraction of flavoproteins become oxidized and, when excited by blue-light, emit green flavoprotein fluorescence (FPF). In this study, we evaluated the utility of FPF as an early indicator of mitochondrial stress, pre-apoptotic cellular instability, and apoptosis of human retinal pigment epithelial (HRPE) cells subjected to hydrogen peroxide (H2O2) or monocytes (unstimulated or interferon-γ-stimulated) in vitro and of freshly isolated pieces of human and rat neural retina subjected to H2O2 ex vivo. Increased FPF of HRPE cells exposed to H2O2 correlated with reduced mitochondrial membrane potential (ΔΨm) and increased apoptosis in a time- and dose-dependent manner. HRPE cells co-cultured with monocytes had increased FPF that correlated in a time-dependent manner with reduced ΔΨm, increased apoptosis, and early expression of pro-inflammatory chemokines, interleukin-8 (IL8) and monocyte chemotactic factor-1 (MCP1), which are known to be induced by oxidative stress. Increased FPF, reduced ΔΨm, and upregulation of IL8 and MCP1 occurred as early as 1–2 hours after exposure to stressors, while apoptosis did not occur in HRPE cells until later time points. The antioxidant, N-aceytl-cysteine (NAC), inhibited increased FPF and apoptosis of HRPE cells subjected to H2O2. Increased FPF of human and rat neural retina also correlated with increased apoptosis. This study suggests that FPF is a useful measure of mitochondrial function in retinal cells and tissues and can detect early mitochondrial dysfunction that may precede apoptosis.
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影响因子：
5
作者：
Long, XL;Goldenthal, MJ;Marín-García, J
通讯作者：
Marín-García, J
影响因子：
4.6
作者：
Kina S;Nakasone T;Takemoto H;Matayoshi A;Makishi S;Sunagawa N;Liang F;Phonaphonh T;Sunakawa H
通讯作者：
Sunakawa H
影响因子：
4.4
作者：
Jiang, SN;Moriarty-Craige, SE;Jones, DP
通讯作者：
Jones, DP
影响因子：
4.4
作者：
Bian, ZM;Elner, SG;Elner, VM
通讯作者：
Elner, VM
影响因子：
4.4
作者：
Armstrong, JS;Whiteman, M;Sternberg, P
通讯作者：
Sternberg, P