Identification and characterization of proteins that are differentially expressed in adipose tissue of olanzapine-induced insulin resistance rat by iTRAQ quantitative proteomics
Identification and characterization of proteins that are differentially expressed in adipose tissue of olanzapine-induced insulin resistance rat by iTRAQ quantitative proteomics
复制标题
iTRAQ定量蛋白质组学鉴定和表征奥氮平诱导的胰岛素抵抗大鼠脂肪组织中差异表达的蛋白质
DOI：
10.1016/j.jprot.2019.103570
复制
发表时间：
2020
影响因子：
3.3
通讯作者：
Li Weiyong
中科院分区：
文献类型：
--
作者：
Yang Ni;Yu Liangyu;Deng Yahui;Han Qiangqiang;Wang Jing;Yu Lixiu;Zhai Zhongfang;Li Weiyong
奥氮平通常用于治疗精神分裂症。然而，长期使用奥氮平会引起代谢副作用，如胰岛素抵抗（IR），严重影响患者的生活质量。迫切需要诊断和预后标志物来提高患者的依从性。我们应用同量异位素相对和绝对定量（iTRAQ）标记技术结合二维LC/MS/MS技术鉴定奥氮平诱导的IR大鼠差异表达的蛋白质。从大鼠脂肪组织中共鉴定出3194个蛋白质，筛选出270个差异表达蛋白质，其比值阈值> 1.5倍或< 0.67倍。基于生物信息学分析和文献检索，我们从270个蛋白质组中选择了6个候选蛋白质（MYH 1，MYL 2，Cp，FABP 4，apoA-IV和Ywhaz），并通过western blot验证了这些蛋白质的表达，这些蛋白质的表达与LC-MS/MS结果一致。最后，FABP 4和apoA-IV，这两个新的IR相关蛋白，在本研究中确定的生物学作用，在3 T3-L1细胞进行了验证。这些数据表明，这两种蛋白通过IRS-1/AKT信号通路作用于奥氮平诱导的IR。我们的研究结果提供了一个数据集的潜在目标，以探讨机制，在奥氮平诱导的IR和揭示新的角色，FABP 4和apoA-IV在奥氮平诱导的IR. Significance：本研究的蛋白质组学分析揭示了目标与奥氮平诱导的IR和提供相关的见解，在这些目标的分子功能，生物学过程和信号通路。MYH 1、MYL 2、Cp、FABP 4、apoA-IV和Ywhaz蛋白可能是潜在的生物标志物，而FABP 4和apoA-IV蛋白被认为是奥氮平诱导IR的潜在靶点，因此，如果进一步证实这些蛋白的生物标志物的性能，这些蛋白将为探讨奥氮平诱导IR的机制提供有力的靶点。
Olanzapine is commonly used to treat schizophrenia. However, long-term administration of olanzapine causes metabolic side effects, such as insulin resistance (IR), which seriously affects patients' quality of life. Both diagnostic and prognostic markers are urgently needed to increase patient compliance. We applied isobaric tags for relative and absolute quantitation (iTRAQ) labeling combined with 2D LC/MS/MS technology to identify the differentially expressed proteins in olanzapine-induced IR rats. A total of 3194 proteins were identified from rat adipose tissues, and 270 differentially expressed proteins were screened out with a ratio threshold > 1.5-fold or < 0.67-fold. Based on a bioinformatics analysis and literature search, we selected six candidates (MYH1, MYL2, Cp, FABP4, apoA-IV, and Ywhaz) from a set of 270 proteins and verified these proteins by western blot; the expression of these proteins coincided with the LC-MS/MS results. Finally, the biological roles of FABP4 and apoA-IV, which are two novel IR-related proteins identified in the present study, were verified in 3T3-L1 cells. These data suggest that these two proteins acted on olanzapine-induced IR via the IRS-1/AKT signaling pathway. Our results provide a dataset of potential targets to explore the mechanism in olanzapine-induced IR and reveal the new roles of FABP4 and apoA-IV in olanzapine-induced IR. Significance: The proteomic analysis of this study revealed the target associated with olanzapine-induced IR and provided relevant insights into the molecular functions, biological processes, and signaling pathways in these targets. Protein MYH1, MYL2, Cp, FABP4, apoA-IV, and Ywhaz may be potential biomarkers, and protein FABP4 and apoA-IV were considered as promising targets in olanzapineinduced IR. Therefore, if the performance of the proposed biomarkers is further confirmed, these proteins can provide powerful targets for exploring the mechanism of olanzapine-induced IR.