Cellular and molecular events mediated by docosahexaenoic acid-derived neuroprotectin D1 signaling in photoreceptor cell survival and brain protection.
Cellular and molecular events mediated by docosahexaenoic acid-derived neuroprotectin D1 signaling in photoreceptor cell survival and brain protection.
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DOI：
10.1016/j.plefa.2009.05.024
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发表时间：
2009-08
期刊：
影响因子：
--
通讯作者：
Bazan NG
中科院分区：
文献类型：
--
作者：
Bazan NG
二十二碳六烯酸（DHA）缺乏与产后视力和神经发育受损、认知能力下降、黄斑变性和其他神经退行性疾病有关。DHA是一种omega-3多不饱和脂肪酸酰基链，集中在脑和视网膜的磷脂中，感光细胞的DHA含量是所有细胞膜中最高的。神经保护素D1 （NPD1, 10R， 17s -二羟基-二十二酸- 4z， 7Z, 11E, 13E, 15Z， 19z -六烯酸）的鉴定和表征有助于了解DHA的生物学意义。在氧化应激挑战的人视网膜色素上皮细胞（RPE）、人脑细胞或缺血再灌注的大鼠脑中，NPD1的合成作为维持体内平衡的反应而增强。因此，神经营养素、Aβ肽42 （Aβ42）、钙离子载体A23187、白细胞介素(IL)-1 β或DHA的供应促进了NPD1的合成。NPD1反过来上调Bcl-2家族的抗凋亡蛋白，降低促凋亡Bcl-2家族成员的表达。此外，NPD1抑制IL-1 β刺激的环氧合酶-2 （COX-2）的表达。由于RPE和光感受器在视网膜变性中都受到损伤并死亡，阐明NPD1信号如何促进视网膜细胞存活可能会导致对疾病机制的新理解。在人类神经细胞中，DHA会减弱淀粉样蛋白-β (Aβ)的分泌，导致NPD1的同时形成。NPD1在阿尔茨海默病（AD） CA1海马区被发现减少，但在大脑的其他区域没有。在AD海马CA1区，NPD1生物合成的关键酶，胞质磷脂酶A2 （cPLA2）和15-脂氧合酶（15-LOX）的表达发生改变。NPD1抑制了a β42引发的促炎基因的激活，上调了培养的人脑细胞中编码Bcl-2、Bcl-xl和bcl -1（A1）的抗凋亡基因。总的来说，这些结果支持了NPD1通过诱导抗凋亡和神经保护基因表达程序来促进脑和视网膜细胞存活的概念，这些基因表达程序抑制a β42诱导的神经毒性和其他形式的细胞损伤，从而在衰老过程中促进体内平衡，以及在神经退行性疾病的发生和进展过程中。
Deficiency in docosahexaenoic acid (DHA) is associated with impaired visual and neurological postnatal development, cognitive decline, macular degeneration, and other neurodegenerative diseases. DHA is an omega-3 polyunsaturated fatty acyl chain concentrated in phospholipids of brain and retina, with photoreceptor cells displaying the highest content of DHA of all cell membranes. The identification and characterization of neuroprotectin D1 (NPD1, 10R, 17S-dihydroxy-docosa-4Z, 7Z, 11E, 13E, 15Z, 19Z-hexaenoic acid) contributes to understanding the biological significance of DHA. In oxidative stress-challenged human retinal pigment epithelial (RPE) cells, human brain cells, or rat brains undergoing ischemia-reperfusion, NPD1 synthesis is enhanced as a response for sustaining homeostasis. Thus, neurotrophins, Aβ peptide 42 (Aβ42), calcium ionophore A23187, interleukin (IL)-1 β, or DHA supply enhances NPD1 synthesis. NPD1, in turn, up-regulates the anti-apoptotic proteins of the Bcl-2 family and decreases the expression of pro-apoptotic Bcl-2 family members. Moreover, NPD1 inhibits IL-1 β-stimulated expression of cyclooxygenase-2 (COX-2). Because both RPE and photoreceptors are damaged and then die in retinal degenerations, elucidating how NPD1 signaling contributes to retinal cell survival may lead to a new understanding of disease mechanisms. In human neural cells, DHA attenuates amyloid-β (Aβ) secretion, resulting in concomitant formation of NPD1. NPD1 was found to be reduced in the Alzheimer’s disease (AD) CA1 hippocampal region, but not in other areas of the brain. The expression of key enzymes for NPD1 biosynthesis, cytosolic phospholipase A2 (cPLA2), and 15-lipoxygenase (15-LOX) was found altered in the AD hippocampal CA1 region. NPD1 repressed Aβ42-triggered activation of pro-inflammatory genes and upregulated the anti-apoptotic genes encoding Bcl-2, Bcl-xl, and Bfl-1(A1) in human brain cells in culture. Overall, these results support the concept that NPD1 promotes brain and retina cell survival via the induction of anti-apoptotic and neuroprotective gene-expression programs that suppress Aβ42-induced neurotoxicity and other forms of cell injury, which in turn fosters homeostasis during development in aging, as well as during the initiation and progression of neurodegenerative diseases.
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影响因子：
3.4
作者：
CHEN, HM;ANDERSON, RE
通讯作者：
ANDERSON, RE
影响因子：
--
作者：
CRAPPER, DR;DALTON, AJ;HACHINSKI, VC
通讯作者：
HACHINSKI, VC
影响因子：
4.8
作者：
Ershov, AV;Lukiw, WJ;Bazan, NG
通讯作者：
Bazan, NG
DOI：
10.1016/0006-291x(84)90601-6
发表时间：
1984-01-01
影响因子：
3.1
作者：
BAZAN, NG;BIRKLE, DL;REDDY, TS
通讯作者：
REDDY, TS
影响因子：
2
作者：
Ershov, AV;Parkins, N;Bazan, NG
通讯作者：
Bazan, NG