Chiglitazar Preferentially Regulates Gene Expression via Configuration-Restricted Binding and Phosphorylation Inhibition of PPARγ

المؤلفون المشاركون

Lu, X. P.
Wang, Wei
Liu, Nan-Song
Yang, Qian-Jiao
Zhang, Kun
Zhu, Jing-Zhong
Huang, Laiqiang
Li, Z. B.
Ning, Z. Q.
Shan, S.
Pan, D. S.

المصدر

PPAR Research

العدد

المجلد 2017، العدد 2017 (31 ديسمبر/كانون الأول 2017)، ص ص. 1-16، 16ص.

الناشر

Hindawi Publishing Corporation

تاريخ النشر

2017-09-19

دولة النشر

مصر

عدد الصفحات

16

التخصصات الرئيسية

الأحياء

الملخص EN

Type 2 diabetes mellitus is often treated with insulin-sensitizing drugs called thiazolidinediones (TZD), which improve insulin resistance and glycemic control.

Despite their effectiveness in treating diabetes, these drugs provide little protection from eminent cardiovascular disease associated with diabetes.

Here we demonstrate how chiglitazar, a configuration-restricted non-TZD peroxisome proliferator-activated receptor (PPAR) pan agonist with moderate transcription activity, preferentially regulates ANGPTL4 and PDK4, which are involved in glucose and lipid metabolism.

CDK5-mediated phosphorylation at serine 273 (S273) is a unique regulatory mechanism reserved for PPARγ, and this event is linked to insulin resistance in type 2 diabetes mellitus.

Our data demonstrates that chiglitazar modulates gene expression differently from two TZDs, rosiglitazone and pioglitazone, via its configuration-restricted binding and phosphorylation inhibition of PPARγ.

Chiglitazar induced significantly greater expression of ANGPTL4 and PDK4 than rosiglitazone and pioglitazone in different cell models.

These increased expressions were dependent on the phosphorylation status of PPARγ at S273.

Furthermore, ChIP and AlphaScreen assays showed that phosphorylation at S273 inhibited promoter binding and cofactor recruitment by PPARγ.

Based on these results, activities from pan agonist chiglitazar can be an effective part of a long-term therapeutic strategy for treating type 2 diabetes in a more balanced action among its targeted organs.

نمط استشهاد جمعية علماء النفس الأمريكية (APA)

Pan, D. S.& Wang, Wei& Liu, Nan-Song& Yang, Qian-Jiao& Zhang, Kun& Zhu, Jing-Zhong…[et al.]. 2017. Chiglitazar Preferentially Regulates Gene Expression via Configuration-Restricted Binding and Phosphorylation Inhibition of PPARγ. PPAR Research،Vol. 2017, no. 2017, pp.1-16.
https://search.emarefa.net/detail/BIM-1197236

نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)

Pan, D. S.…[et al.]. Chiglitazar Preferentially Regulates Gene Expression via Configuration-Restricted Binding and Phosphorylation Inhibition of PPARγ. PPAR Research No. 2017 (2017), pp.1-16.
https://search.emarefa.net/detail/BIM-1197236

نمط استشهاد الجمعية الطبية الأمريكية (AMA)

Pan, D. S.& Wang, Wei& Liu, Nan-Song& Yang, Qian-Jiao& Zhang, Kun& Zhu, Jing-Zhong…[et al.]. Chiglitazar Preferentially Regulates Gene Expression via Configuration-Restricted Binding and Phosphorylation Inhibition of PPARγ. PPAR Research. 2017. Vol. 2017, no. 2017, pp.1-16.
https://search.emarefa.net/detail/BIM-1197236

نوع البيانات

مقالات

لغة النص

الإنجليزية

الملاحظات

Includes bibliographical references

رقم السجل

BIM-1197236