Fibroblast growth factor 2 modulates extracellular purine metabolism by upregulating ecto-5′-nucleotidase and adenosine deaminase in cultured rat spinal cord astrocytes
Fibroblast growth factor 2 modulates extracellular purine metabolism by upregulating ecto-5′-nucleotidase and adenosine deaminase in cultured rat spinal cord astrocytes
复制标题
成纤维细胞生长因子 2 通过上调培养的大鼠脊髓星形胶质细胞中的 5-核酸外切酶和腺苷脱氨酶来调节细胞外嘌呤代谢
DOI：
10.1016/j.jphs.2018.12.002
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发表时间：
2019
影响因子：
3.5
通讯作者：
Otsuguro Ken-ichi
中科院分区：
文献类型：
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作者：
Eguchi Ryota;Yamaguchi Soichiro;Otsuguro Ken-ichi
通过星形胶质细胞产生的ATP和腺苷的嘌呤能信号传导是中枢神经系统（CNS）中神经元-胶质细胞相互作用的基础途径之一。在嘌呤的生产中，通过胞外酶释放的嘌呤的胞外代谢是重要的。这些酶的表达和活性在病理条件下改变。成纤维细胞生长因子2（FGF 2）的产生在病理条件下增加，并且这对星形胶质细胞具有各种影响。在这里，我们研究了FGF 2对培养的大鼠脊髓星形胶质细胞嘌呤代谢的影响。星形胶质细胞迅速代谢嘌呤添加到细胞外溶液。FGF 2通过上调腺苷脱氨酶（ADA）和腺苷5′-核苷酸酶（5′-nucleotidase，5 ′-nucleotide，5 ′-n在星形胶质细胞的胞液和外液中均检测到ADA活性和蛋白，并且其水平被FGF 2显著增加。FGF 2还增加内源性释放的ATP的代谢，导致腺苷的瞬时增加和细胞外肌苷的大量积累。此外，FGF 2通过上调间隙连接半通道的活性来增加ATP释放。这些数据表明，FGF 2调节星形胶质细胞中嘌呤的产生，并表明星形胶质细胞释放的细胞外ADA在CNS中细胞外嘌呤代谢中起重要作用。
Purinergic signaling via ATP and adenosine produced by astrocytes is one pathway underlying neuron–glia interactions in the central nervous system (CNS). In production of purines, extracellular metabolism of released purines via ecto-enzymes is important. The expression and activities of these enzymes are altered under pathological conditions. Production of fibroblast growth factor 2 (FGF2) is increased under pathological conditions, and this has various effects on astrocytes. Here, we investigated the effects of FGF2 on purine metabolism in cultured rat spinal cord astrocytes. Astrocytes rapidly metabolized purines added to the extracellular solution. FGF2 increased extracellular metabolism of AMP to adenosine and of adenosine to inosine by upregulating ecto-5′-nucleotidase and adenosine deaminase (ADA), respectively. ADA activity and protein were detected both in the cytosol and external solution of astrocytes, and their levels were markedly increased by FGF2. FGF2 also increased metabolism of endogenously released ATP, resulting in a transient increase in adenosine and substantial accumulation of extracellular inosine. Moreover, FGF2 increased ATP release by upregulating the activity of gap junction hemichannels. These data show that FGF2 regulates purine production in astrocytes and suggest that extracellular ADA released by astrocytes plays an important role in extracellular purine metabolism in the CNS.