title: Association of downregulated HDAC 2 with the impaired mitochondrial function and cytokine secretion in the monocytes/macrophages from gestational diabetes mellitus patients.
abstract: Gestational diabetes mellitus (GDM) is associated with an increased risk of type 2 diabetes (T2DM) and cardiovascular diseases in later life, yet with underlying mechanisms unclear. The present study was to explore the association of upregulated histone deacetylase 2 (HDAC 2) with the impaired mitochondrial function and the cytokine secretion in the monocytes/macrophages from GDM patients. In this study, we examined the mitochondrial function, proinflamatory cytokine secretion and the HDAC 2 level in the serum or in the monocytes/macrophages from GDM patients, investigated the influence by HDAC 2 inhibitor, AR-42 (N-hydroxy-4-[[(2S)-3-methyl-2-phenylbutanoyl]amino]benzamide), on the mitochondrial function and cytokine secretion in the isolated GDM monocytes/macrophages. Results demonstrated an increased mitochondria size, mitochondrial superoxide and reactive oxygen species (ROS) production, and an undermined mitochondria membrane potential (MMP) in the GDM monocytes/macrophages. And the serum levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 were also markedly higher in the GDM pregnancies, while the expression and activity of HDAC 2 was downregulated. Moreover, AR-42-mediated HDAC 2 inhibition in vitro contributed to the impaired mitochondrial function and the proinflamatory cytokine secretion. In conclusion, this study suggests an association of the impaired mitochondrial function and the promoted proinflamatory cytokine secretion with the reduced HDAC 2 activity in GDM. These findings may present HDAC 2 as a target for GDM treatment.
authors.affiliation: Department of Obstetrics and Gynecology, the Affiliated Yantai Yuhuangding Hospital of Medical College, Qingdao University, Yantai 264000, Shandong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Ultrasonography, the Affiliated Yantai Yuhuangding Hospital of Medical College, Qingdao University, Yantai 264000, Shandong, China.
authors.forename: Hongna
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Obstetrics and Gynecology, the Affiliated Yantai Yuhuangding Hospital of Medical College, Qingdao University, Yantai 264000, Shandong, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Jia
authors.affiliation: Department of Obstetrics and Gynecology, the Affiliated Yantai Yuhuangding Hospital of Medical College, Qingdao University, Yantai 264000, Shandong, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Obstetrics and Gynecology, the Affiliated Yantai Yuhuangding Hospital of Medical College, Qingdao University, Yantai 264000, Shandong, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Obstetrics and Gynecology, the Affiliated Yantai Yuhuangding Hospital of Medical College, Qingdao University, Yantai 264000, Shandong, China.
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Clinical laboratory, the Affiliated Yantai Yuhuangding Hospital of Medical College, Qingdao University, Yantai 264000, Shandong, China.
authors.forename: Chengming
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, the Affiliated Yantai Yuhuangding Hospital of Medical College, Qingdao University, Yantai 264000, Shandong, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Chu
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D016640:Diabetes, Gestational / Q000097:blood* / Q000201:enzymology / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D056464:Histone Deacetylase 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D010654:Phenylbutyrates / Q000494:pharmacology; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D053583:Interleukin-1beta; D015850:Interleukin-6; C529674:OSU-HDAC42 compound; D010654:Phenylbutyrates; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2
keywords: gestational diabetes mellitus (GDM); histone deacetylase (HDAC) 2; mitochondrial dysfunction (MD); monocytes/macrophages; proinflamatory cytokine