Ameliorative effects of indomethacin at different concentrations on endothelial insulin resistance through two distinct pathways

Xian, Tao; Gan, Yuyang; Lü, Yi; Wang, Mengxi; Yuan, Wanwan; Zhou, Yixin; Chen, Junye; Wang, Kun; Xiong, Shaofeng; Huang, Qiren

doi:10.1016/j.biopha.2018.07.069

Cited by 1 publication

(1 citation statement)

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“…Thus, the endothelium IR model was successfully established and applied to the subsequent research. While the respective effects of high glucose and high PA were shown, their combination effects (synergistic effects) were not displayed in the present study, which has been characterized in our recent study (Xian et al, 2018).…”

Section: Identification Of Pias1 Silencing Efficiencycontrasting

confidence: 55%

Sumoylation of PPARγ contributes to vascular endothelium insulin resistance through stabilizing the PPARγ–NcoR complex

Lan

Shen

Yuan

et al. 2019

Journal Cellular Physiology

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Sumoylation of peroxisome proliferator-activated receptor γ (PPARγ) affects its stabilization, sublocalization, and transcriptional activity. However, it remains largely unknown whether PPARγ sumoylation inhibits the transactivation effect, leading to endothelium insulin resistance (IR). To test this possibility, human umbilical vascular endothelial cells (HUVECs) with a 90% confluence were randomly allocated to two batches. One batch was first pretreated with or without vitamin E for 24 hr and the other infected with adenoviruses containing either PIAS1-shRNA (protein inhibitor of activated STAT1-short hairpin RNA) or scramble shRNA. Cells were suffered from high glucose and palmitic acid (PA) exposure for further 48 hr. The levels of PPARγ, p-IKK, IKK, and NcoR (nuclear corepressors) were measured by western blot analysis.The interaction of IKK and PIAS1, as well as the PPARγ sumoylation, were examined by coimmunoprecipitation. The results showed that the exposure of high glucose and PA induced reactive oxygen species (ROS) production and IKK activation in HUVECs, promoting the interaction of IKK and PIAS1 and the sumoylation of PPARγ. However, vitamin E and PIAS1-shRNA partially decreased ROS production and IKK activation induced by high glucose and PA exposure. These data indicate that ROS-IKK-PIAS1 pathway mediates PPARγ sumoylation, leading to endothelium IR via stabilizing PPARγ-NcoR complex. These findings benefit understanding of regulatory networks of insulin signaling, which might provide a potential target to prevent and cure IRrelated diseases.

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Section: Identification Of Pias1 Silencing Efficiencycontrasting

confidence: 55%