p62-mediated autophagy affects nutrition-dependent insulin receptor substrate 1 dynamics in 3T3-L1 preadipocytes.
p62-mediated autophagy affects nutrition-dependent insulin receptor substrate 1 dynamics in 3T3-L1 preadipocytes.
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DOI：
10.1111/jdi.12866
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发表时间：
2019-01
影响因子：
3.2
通讯作者：
Takamura T
中科院分区：
文献类型：
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作者：
Igawa H;Kikuchi A;Misu H;Ishii KA;Kaneko S;Takamura T
先前的研究表明，生物体的营养状况会以组织特异性的方式改变胰岛素受体底物 1 (IRS-1) 的蛋白质水平。尽管 IRS-1 在与糖尿病和胰岛素抵抗相关的营养丰富条件下的调节机制已得到充分研究，但在营养贫乏条件下的调节机制仍不清楚。本研究的目的是研究 IRS-1 蛋白水平如何根据 3T3-L1 前脂肪细胞的营养状况而变化。 3T3-L1 前脂肪细胞用无葡萄糖、无氨基酸和无血清培养基进行饥饿处理。通过蛋白质印迹法检测IRS-1蛋白水平。通过蛋白质印迹和荧光显微镜观察自噬活性。通过蛋白质印迹和免疫细胞化学检查了饥饿条件下自噬和 p62（选择性自噬的接头）对 IRS-1 蛋白水平的影响。我们发现，当饥饿激活自噬时，IRS-1 的水平下降，但胰岛素受体和蛋白激酶 B 的水平没有下降。氯喹或自噬相关 7 (Atg7) 核糖核酸干扰对自噬的抑制抵消了饥饿引起的 IRS-1 的减少。此外，Atg7 敲低会增加饥饿条件下胰岛素刺激的蛋白激酶 B 的磷酸化。此外，在饥饿条件下，p62 与 IRS-1 共定位，p62 敲低抵消了饥饿诱导的 IRS-1 降解。通过 p62 的自噬在调节 IRS-1 蛋白水平以应对营养缺乏方面发挥着重要作用。目前的研究结果表明，自噬可能作为能量消耗感知机制，可以微调胰岛素信号转导。
Previous studies have shown that an organism's nutritional status changes the protein levels of insulin receptor substrate 1 (IRS‐1) in a tissue‐specific manner. Although the mechanisms underlying the regulation of IRS‐1 in the nutrient‐rich conditions associated with diabetes and insulin resistance have been well studied, those under nutrient‐poor conditions remain unknown. The aim of the present study was to investigate how IRS‐1 protein levels change depending on the nutritional status of 3T3‐L1 preadipocytes. 3T3‐L1 preadipocytes were treated with glucose‐, amino acid‐ and serum‐free medium for starvation. IRS‐1 protein levels were detected by western blot. Autophagy activity was observed by western blot and fluorescence microscopy. The effect of autophagy and p62, an adaptor for selective autophagy, on IRS‐1 protein levels under starvation conditions was examined by western blot and immunocytochemistry. We showed that the levels of IRS‐1, but not those of insulin receptor and protein kinase B, decreased when starvation activated autophagy. The inhibition of autophagy by chloroquine or autophagy‐related 7 (Atg7) ribonucleic acid interference counteracted the starvation‐induced decrease of IRS‐1. Additionally, Atg7 knockdown increased insulin‐stimulated phosphorylation of protein kinase B under starvation conditions. Furthermore, p62 colocalized with IRS‐1 under starvation conditions, and p62 knockdown counteracted the starvation‐induced degradation of IRS‐1. Autophagy through p62 plays an important role in regulating IRS‐1 protein levels in response to nutritional deficiency. The present findings suggest that autophagy might function as energy depletion‐sensing machinery that finely tunes insulin signal transduction.
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影响因子：
7.7
作者：
Otoda T;Takamura T;Misu H;Ota T;Murata S;Hayashi H;Takayama H;Kikuchi A;Kanamori T;Shima KR;Lan F;Takeda T;Kurita S;Ishikura K;Kita Y;Iwayama K;Kato K;Uno M;Takeshita Y;Yamamoto M;Tokuyama K;Iseki S;Tanaka K;Kaneko S
通讯作者：
Kaneko S
DOI：
10.1073/pnas.77.1.285
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
REED, BC;LANE, MD
通讯作者：
LANE, MD
影响因子：
7.7
作者：
Pederson, TM;Kramer, DL;Rondinone, CM
通讯作者：
Rondinone, CM
影响因子：
7.7
作者：
Friedman, JE;Ishizuka, T;Catalano, P
通讯作者：
Catalano, P
p62/SQSTM1形成自噬降解的蛋白质聚集体，并对亨廷顿蛋白诱导的细胞死亡具有保护作用。
影响因子：
7.8
作者：
Bjorkoy, Geir;Lamark, Trond;Brech, Andreas;Outzen, Heidi;Perander, Maria;Overvatn, Aud;Stenmark, Harald;Johansen, Terje
通讯作者：
Johansen, Terje