Oxidative stress regulates type 3 deiodinase and type 2 deiodinase in cultured rat astrocytes
Oxidative stress regulates type 3 deiodinase and type 2 deiodinase in cultured rat astrocytes
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DOI：
10.1210/en.2007-1462
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发表时间：
2008-07-01
期刊：
影响因子：
4.8
通讯作者：
Courtin, Francoise
中科院分区：
文献类型：
--
作者：
Lamirand, Audrey;Pallud-Mothre, Sophie;Courtin, Francoise
2型脱碘酶（D2）和3型脱碘酶（D3）局部实现T-3浓度的测定，T-3以高亲和力结合甲状腺激素受体。D2将T-4转化为T-3，D3降解T-4和T-3。神经元摄取星形胶质细胞释放的T-3，星形胶质细胞是D2表达的主要大脑部位。由于氧化应激被认为是参与了一些神经系统疾病，我们探讨了氧化应激对D3和D2在大鼠星形胶质细胞的原代培养的影响。H_2O_2（250 μ M）可增加D_3活性，作用最大时约为8h。通过H2 O2刺激D3活性与T-4、佛波酯和cAMP具有协同作用。H2 O2（250 μ M）不影响基础D2活性，但抑制刺激D2活性的cAMP和因素牵连cAMP-独立的途径，在星形胶质细胞，促甲状腺激素，佛波酯。N-乙酰半胱氨酸和硒的补充，分别增加细胞内谷胱甘肽和谷胱甘肽过氧化物酶，抑制D2和D3的调节H2 O2，而L-丁硫氨酸亚砜亚胺，减少细胞内谷胱甘肽，模仿H2 O2的影响。氧化应激通过转录机制上调D3并抑制cAMP刺激的D2。氧化应激引起的cAMP减少可能有助于抑制cAMP刺激的D2。使用特定的信号通路抑制剂，我们表明，ERK通路所需的D2和D3的调节氧化应激和p38 MAPK通路有牵连H2 O2诱导的D3。我们认为，预期的减少T-3可能会调节细胞损伤的氧化应激在某些病理性脑条件。
Type 2 deiodinase (D2) and type 3 deiodinase (D3) locally achieve the determination of the concentration of T-3, which binds to the thyroid hormone receptor with high affinity. D2 converts T-4 into T-3, and D3 degrades T-4 and T-3. Neurons take up T-3 released by astrocytes, the main cerebral site for the D2 expression. Because oxidative stress is believed to be involved in several neurological disorders, we explored the effects of oxidative stress on D3 and D2 in primary culture of rat astrocytes. H2O2 (250 mu M) increased D3 activity with maximal effects around 8 h. Stimulation of D3 activity by H2O2 was synergistic with T-4, phorbol ester, and also cAMP. H2O2 (250 mu M) did not affect basal D2 activity but inhibited the stimulation of D2 activity by cAMP and factors implicating cAMP-independent pathways in astrocytes, TSH, and phorbol ester. N-Acetyl cysteine and selenium repletion, which respectively increase intracellular glutathione and glutathione peroxidase, inhibited D2 and D3 regulation by H2O2, whereas L-buthionine sulfoximine, which decreases intracellular glutathione, mimicked H2O2 effects. Oxidative stress up-regulated D3 and inhibited cAMP-stimulated D2 by transcriptional mechanisms. A decrease in cAMP by oxidative stress could contribute to the inhibition of cAMP-stimulated D2. Using specific inhibitors of signaling pathways, we show that the ERK pathway was required in D2 and D3 regulation by oxidative stress and that the p38 MAPK pathway was implicated in H2O2-induced D3. We suggest that the expected decrease in T-3 might modulate the cellular injury of oxidative stress in some pathological brain conditions.