Sumoylation of PPAR? contributes to vascular endothelium insulin resistance through stabilizing the PPAR?-NcoR complex.
Sumoylation of peroxisome proliferator-activated receptor ? (PPAR?) affects its stabilization, sublocalization, and transcriptional activity. However, it remains largely unknown whether PPAR? 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 PPAR?, p-IKK, IKK, and NcoR (nuclear corepressors) were measured by western blot analysis. The interaction of IKK and PIAS1, as well as the PPAR? 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 PPAR?. 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 PPAR? sumoylation, leading to endothelium IR via stabilizing PPAR?-NcoR complex. These findings benefit understanding of regulatory networks of insulin signaling, which might provide a potential target to prevent and cure IR-related diseases.
Mesh Terms:
Endothelium, Vascular, Gene Regulatory Networks, Glucose, Human Umbilical Vein Endothelial Cells, Humans, Insulin, Insulin Resistance, Multiprotein Complexes, Nuclear Receptor Co-Repressor 1, PPAR gamma, Palmitic Acid, Protein Inhibitors of Activated STAT, RNA, Small Interfering, Reactive Oxygen Species, STAT1 Transcription Factor, Signal Transduction, Small Ubiquitin-Related Modifier Proteins, Sumoylation, Vitamin E
Endothelium, Vascular, Gene Regulatory Networks, Glucose, Human Umbilical Vein Endothelial Cells, Humans, Insulin, Insulin Resistance, Multiprotein Complexes, Nuclear Receptor Co-Repressor 1, PPAR gamma, Palmitic Acid, Protein Inhibitors of Activated STAT, RNA, Small Interfering, Reactive Oxygen Species, STAT1 Transcription Factor, Signal Transduction, Small Ubiquitin-Related Modifier Proteins, Sumoylation, Vitamin E
J Cell Physiol
Date: Dec. 01, 2018
PubMed ID: 30982983
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