Upregulation of Myelin Gene Expression by a Physically-Modified Saline via Phosphatidylinositol 3-Kinase-Mediated Activation of CREB: Implications for Multiple Sclerosis.
Upregulation of Myelin Gene Expression by a Physically-Modified Saline via Phosphatidylinositol 3-Kinase-Mediated Activation of CREB: Implications for Multiple Sclerosis.
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DOI：
10.1007/s11064-017-2435-1
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发表时间：
2018-03
影响因子：
4.4
通讯作者：
Pahan K
中科院分区：
文献类型：
--
作者：
Jana M;Ghosh S;Pahan K
中枢神经系统（CNS）髓鞘再生的增加和CNS炎症的减少是阻止多发性硬化（MS）进展的重要步骤。RNS 60是通过在升高的氧气压力下使生理盐水经受Taylor-Couette-Poiffille流而产生的生物活性水溶液。最近，我们已经证明RNS 60具有抗炎特性。在这里，我们描述了RNS 60的髓鞘形成特性。RNS 60，而不是生理盐水（NS），RNS10.3（TCP修饰的盐水，没有过量的氧气）或PNS 60（盐水含有过量的氧气，没有TCP修饰），刺激髓鞘特异性基因和蛋白质（髓鞘碱性蛋白，MBP;髓鞘少突胶质细胞糖蛋白，MOG和蛋白脂质蛋白，PLP）在原代小鼠少突胶质细胞和混合神经胶质细胞的表达。在研究机制的同时，我们发现RNS 60处理诱导了少突胶质细胞中cAMP反应元件结合蛋白（CREB）的激活，最终导致CREB被募集到髓鞘特异性基因的启动子中。此外，1A型p110β/α的激活，而不是1B型p110γ，RNS 60对磷脂酰肌醇-3（PI-3）激酶的抑制作用以及LY 294002对RNS 60介导的CREB激活和髓磷脂基因上调的抑制作用（PI-3激酶的特异性抑制剂）表明RNS 60上调CREB的激活和髓磷脂-β-D-受体的表达。通过激活PI 3激酶在少突胶质细胞中的特异性分子。这些结果突出了RNS 60的一种新的前髓鞘形成特性，这可能对MS和其他脱髓鞘疾病有益。
An increase in central nervous system (CNS) remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis (MS). RNS60 is a bioactive aqueous solution generated by subjecting normal saline to Taylor–Couette–Poiseuille flow under elevated oxygen pressure. Recently we have demonstrated that RNS60 exhibits anti-inflammatory properties. Here, we describe promyelinating property of RNS60. RNS60, but not normal saline (NS), RNS10.3 (TCP-modified saline without excess oxygen) or PNS60 (saline containing excess oxygen without TCP modification), stimulated the expression of myelin-specific genes and proteins (myelin basic protein, MBP; myelin oligodendrocyte glycoprotein, MOG and proteolipid protein, PLP) in primary mouse oligodendroglia and mixed glial cells. While investigating the mechanisms, we found that RNS60 treatment induced the activation of cAMP response element binding protein (CREB) in oligodendrocytes, ultimately leading to the recruitment of CREB to the promoters of myelin-specific genes. Furthermore, activation of type 1A p110β/α, but not type 1B p110γ, phosphatidylinositol-3 (PI-3) kinase by RNS60 together with abrogation of RNS60-mediated activation of CREB and upregulation of myelin genes by LY294002 (a specific inhibitor of PI-3 kinase) suggest that RNS60 upregulates the activation of CREB and the expression of myelin-specific molecules in oligodendrocytes via activation of PI3 kinase. These results highlight a novel promyelinating property of RNS60, which may be of benefit for MS and other demyelinating disorders.
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影响因子：
3
作者：
Garat CV;Crossno JT Jr;Sullivan TM;Reusch JE;Klemm DJ
通讯作者：
Klemm DJ
DOI：
10.4049/jimmunol.1102624
发表时间：
2012-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Corbett GT;Roy A;Pahan K
通讯作者：
Pahan K
影响因子：
3.6
作者：
Jana M;Pahan K
通讯作者：
Pahan K
影响因子：
4.2
作者：
Garcia, C;Paez, P;Pasquini, JM
通讯作者：
Pasquini, JM
影响因子：
4.4
作者：
Jana, Malabendu;Jana, Arundhati;Pahan, Kalipada
通讯作者：
Pahan, Kalipada