Activation of PPAR-γ by Pioglitazone Attenuates Oxidative Stress in Aging Rat Cerebral Arteries Through Upregulating UCP2

Wang, Peijian; Li, Bing-Hu; Cai, Guocai; Huang, Mingqing; Jiang, Licheng; Jing, Pu; Li, Lü; Wu, Qi; Zuo, Li; Wang, Qiulin; Zhou, Peng

doi:10.1097/fjc.0000000000000143

Cited by 28 publications

(14 citation statements)

References 37 publications

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“…PPARγ, a member of PPAR superfamily, is mainly expressed in adipocytes and activates both lipogenic and lipid oxidation [ 28 ]. Reportedly, PPARγ activation attenuated ROS production in aging rat cerebral arteries and human umbilical vein endothelial cells [ 29 ]. Our previous study showed that PPARγ attenuated carotid arteries IH by inhibiting TLR4-mediated inflammation in VSMCs [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Chuang et al showed that activation of PPARγ by RSG enhanced UCP2 expression and further protected against oxidative stress and neuronal cell death associated with cerebral ischemia [ 38 ]. Wang et al showed that activation of PPARγ by pioglitazone attenuated oxidative stress in aging rat cerebral arteries through upregulating UCP2 [ 29 ]. However, it is still unknown whether PPARγ exerts antioxidant effect through upregulating UCP2 in PDGF-BB or wire injury induced VSMC proliferation and migration.…”

Section: Discussionmentioning

confidence: 99%

“…Among the members of UCPs, UCP2 is considered to be important to protect against oxidative stress [ 9 , 16 , 17 ]. Moreover, activation of PPARγ against oxidative damage in aging cerebral arteries is involved with upregulating UCP2 [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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PPARγ Inhibits VSMC Proliferation and Migration via Attenuating Oxidative Stress through Upregulating UCP2

Zhou

Zhang

et al. 2016

PLoS ONE

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Increasing evidence showed that abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are common event in the pathophysiology of many vascular diseases, including atherosclerosis and restenosis after angioplasty. Among the underlying mechanisms, oxidative stress is one of the principal contributors to the proliferation and migration of VSMCs. Oxidative stress occurs as a result of persistent production of reactive oxygen species (ROS). Recently, the protective effects of peroxisome proliferator-activated receptor γ (PPARγ) against oxidative stress/ROS in other cell types provide new insights to inhibit the suggests that PPARγ may regulate VSMCs function. However, it remains unclear whether activation of PPARγ can attenuate oxidative stress and further inhibit VSMC proliferation and migration. In this study, we therefore investigated the effect of PPARγ on inhibiting VSMC oxidative stress and the capability of proliferation and migration, and the potential role of mitochondrial uncoupling protein 2 (UCP2) in oxidative stress. It was found that platelet derived growth factor-BB (PDGF-BB) induced VSMC proliferation and migration as well as ROS production; PPARγ inhibited PDGF-BB-induced VSMC proliferation, migration and oxidative stress; PPARγ activation upregulated UCP2 expression in VSMCs; PPARγ inhibited PDGF-BB-induced ROS in VSMCs by upregulating UCP2 expression; PPARγ ameliorated injury-induced oxidative stress and intimal hyperplasia (IH) in UCP2-dependent manner. In conclusion, our study provides evidence that activation of PPARγ can attenuate ROS and VSMC proliferation and migration by upregulating UCP2 expression, and thus inhibit IH following carotid injury. These findings suggest PPARγ may represent a prospective target for the prevention and treatment of IH-associated vascular diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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PPARγ Inhibits VSMC Proliferation and Migration via Attenuating Oxidative Stress through Upregulating UCP2

Zhou

Zhang

et al. 2016

PLoS ONE

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“…The precise biochemical function of mitochondrial UCP2 is still a matter of debate. Accumulating literatures have showed that UCP2 plays a positive physiological role by regulating mitochondrial biogenesis, maintaining energy balance, keeping calcium homeostasis [ 11 ], ROS elimination [ 12 ], and regulating cellular autophagy [ 13 ] and, thereby, provides cellular protection and possibly anti-aging [ 14 ]. But some other studies that used inhibitors, knockdown, or mutagenesis methods indicated UCP2 might have many deleterious effects and were involved in pathogenesis of numerous diseases, such as cardiovascular diseases [ 15 ], type 2 diabetes mellitus [ 8 ], obesity [ 16 ], polycystic ovary syndrome (PCOS) [ 17 ], and various cancers [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Mitochondrial Uncoupling Protein 2 Inhibition by Genipin in Human Cumulus Cells

Zhang

Shan

et al. 2015

BioMed Research International

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UCP2 plays a physiological role by regulating mitochondrial biogenesis, maintaining energy balance, ROS elimination, and regulating cellular autophagy in numerous tissues. But the exact roles of UCP2 in cumulus cells are still not clear. Genipin, a special UCP2 inhibitor, was added into the cultural medium to explore the roles of UCP2 in human cumulus cells. There were no significant differences in ATP and mitochondrial membrane potential levels in cumulus cells from UCP2 inhibiting groups as compared with the control. The levels of ROS and Mn-SOD were markedly elevated after UCP2 inhibited Genipin. However, the ratio of reduced GSH to GSSG significantly declined after treatment with Genipin. UCP2 inhibition by Genipin also resulted in obvious increase in the active caspase-3, which accompanied the decline of caspase-3 mRNA. The level of progesterone in culture medium declined obviously after Genipin treatment. But there was no significant difference in estradiol concentrations. This study indicated that UCP2 is expressed in human cumulus cells and plays important roles on mediate ROS production, apoptotic process, and steroidogenesis, suggesting UCP2 may be involved in regulation of follicle development and oocyte maturation and quality.

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“…For example, there is evidence to reveal that PPAR expression is inversely correlated with inflammatory cytokines IL-1β and TNF-α in aging rats (Gelinas & Mclaurin 2005). The PPARγ agonist ameliorates aging-related renal and cerebral artery injuries by inhibiting the inflammatory genes, reducing ECM production, and attenuating oxidative stress (Sung et al 2006;Wang et al 2014;Yang et al 2009). In this study, we also found PPARγ was downregulated in the cochlear tissues of Cmah-null mice and our PPI network showed PPARG could interact with SOD2, FOS and ICAM1, implying PPARG mediated pathways may be also a considerably important mechanism for AHL and activation of PPARG may be an underlying therapeutic method for patients with AHL, which has not been reported previously.…”

Section: Discussionmentioning

confidence: 99%

Peer Review #2 of "Cmah deficiency may lead to age-related hearing loss by influencing miRNA-PPAR mediated signaling pathway (v0.1)"

2019

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Background: Previous evidence has indicated CMP-Neu5Ac hydroxylase (Cmah) disruption inducesaging-related hearing loss (AHL). However, its function mechanisms remain unclear. This study was to explore the mechanisms of AHL by using microarray analysis in the Cmah deficiency animal model. Methods: Microarray dataset GSE70659 was available from the Gene Expression Omnibus database, including cochlear tissues from wild-type and Cmah-null C57BL/6J mice with old age (12 months, n = 3). Differentially expressed genes (DEGs) were identified using the Linear Models for Microarray data method and protein-protein interaction (PPI) network was constructed using data from the Search Tool for the Retrieval of Interacting Genes database followed by module analysis. Kyoto encyclopedia of genes and genomes pathway enrichment analysis was performed using The Database for Annotation, Visualization and Integrated Discovery. The upstream miRNAs and potential small-molecule drugs were predicted by miRwalk2.0 and Connectivity Map, respectively. Results: A total of 799 DEGs (449 upregulated and 350 downregulated) were identified. Upregulated DEGs were involved in Cell adhesion molecules (ICAM1, intercellular adhesion molecule 1) and tumor necrosis factor (TNF) signaling pathway (FOS, FBJ osteosarcoma oncogene; ICAM1), while downregulated DEGs participated in PPAR signaling pathway (PPARG, peroxisome proliferator-activated receptor gamma). A PPI network was constructed, in which FOS, ICAM1 and PPARG were ranked as hub genes and PPARG was a transcription factor to regulate other target genes (ICAM1, FOS). Function analysis of two significant modules further demonstrated PPAR signaling pathway was especially important. Furthermore, mmu-miR-130b-3p, mmu-miR-27a-3p, mmu-miR-27b-3p and mmu-miR-721 were predicted to regulate PPARG. Topiramate were speculated to be a potential small-molecule drug to reverse DEGs in AHL. Conclusions: PPAR mediated signaling pathway may be an important mechanism for AHL. Downregulation of the above miRNAs and use of topiramate may be potential treatment

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Activation of PPAR-γ by Pioglitazone Attenuates Oxidative Stress in Aging Rat Cerebral Arteries Through Upregulating UCP2

Cited by 28 publications

References 37 publications

PPARγ Inhibits VSMC Proliferation and Migration via Attenuating Oxidative Stress through Upregulating UCP2

PPARγ Inhibits VSMC Proliferation and Migration via Attenuating Oxidative Stress through Upregulating UCP2

Effects of Mitochondrial Uncoupling Protein 2 Inhibition by Genipin in Human Cumulus Cells

Peer Review #2 of "Cmah deficiency may lead to age-related hearing loss by influencing miRNA-PPAR mediated signaling pathway (v0.1)"

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