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Glucocorticoids negatively regulates chaperone mediated autophagy and microautophagy.
Biochemical and Biophysical Research Communications ( IF 3.1 ) Pub Date : 2020-05-30 , DOI: 10.1016/j.bbrc.2020.04.132
Masahiro Sato 1 , Erika Ueda 2 , Ayumu Konno 3 , Hirokazu Hirai 3 , Yuki Kurauchi 2 , Akinori Hisatsune 2 , Hiroshi Katsuki 2 , Takahiro Seki 2
Affiliation  

Glucocorticoids are released from the adrenal cortex and are important for regulating various physiological functions. However, a persistent increase in glucocorticoids due to chronic stress causes various dysfunctions in the central nervous system which can lead to mental disorders such as depression. Macroautophagy, one of the pathways of the autophagy-lysosome protein degradation system, is dysregulated in psychiatric disorders, implicating a disturbance of protein degradation in the pathogenesis of psychiatric disorders. In the present study, we investigated whether glucocorticoids affect the activity of chaperone-mediated autophagy (CMA) and microautophagy (mA), the other two pathways of the autophagy-lysosome system. Treatment of human-derived AD293 cells and primary cultured rat cortical neurons with dexamethasone, a potent glucocorticoid receptor agonist, and endogenous glucocorticoids decreased both CMA and mA activities. However, this decrease was significantly suppressed by treatment with RU-486, a glucocorticoid receptor antagonist. In addition, dexamethasone significantly decreased lysosomal Hsc70. These findings suggest that glucocorticoids negatively regulate CMA and mA in a glucocorticoid receptor-dependent manner, and provide evidence for CMA and mA as novel therapeutic targets for depression.



中文翻译:

糖皮质激素负调节伴侣介导的自噬和微自噬。

糖皮质激素从肾上腺皮质释放,对于调节各种生理功能很重要。然而,由于慢性应激引起的糖皮质激素的持续增加会引起中枢神经系统的各种功能障碍,从而导致精神疾病,例如抑郁。巨自噬是自噬-溶酶体蛋白质降解系统的一种途径,在精神疾病中失调,这暗示着蛋白质降解在精神疾病的发病机理中的作用。在本研究中,我们调查了糖皮质激素是否影响伴侣介导的自噬(CMA)和微自噬(mA)(自噬-溶酶体系统的其他两个途径)的活性。地塞米松治疗人源性AD293细胞和原代培养的大鼠皮质神经元 一种有效的糖皮质激素受体激动剂,内源性糖皮质激素降低CMA和mA活性。但是,通过糖皮质激素受体拮抗剂RU-486的治疗可明显抑制这种下降。此外,地塞米松显着降低了溶酶体Hsc70。这些发现表明,糖皮质激素以糖皮质激素受体依赖性方式负调控CMA和mA,并且提供了CMA和mA作为抑郁症的新治疗靶标的证据。

更新日期:2020-05-30
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