Structure and physiological functions of the human peroxisome proliferator-activated receptor γ

Zieleniak, Andrzej; Wójcik, Marzena; Woźniak, Lucyna A.

doi:10.1007/s00005-008-0037-y

Cited by 107 publications

(94 citation statements)

References 159 publications

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“…Similar to other nuclear receptors, PPARs have a conserved structure that includes an N-terminal ligand-independent activation domain, a highly conserved DNAbinding domain, a C-terminal ligand-binding domain, and a Cterminal ligand-dependent activation domain ( Fig. 1) (Chan et al, 2010;Zieleniak et al, 2008). Single amino acid mutations within these functional domains result in severe defects in PPAR function that affect lipid metabolism and insulin resistance (Agostini et al, 2006;Barroso et al, 1999;Hegele et al, 2002;Ristow et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases

Choi¹,

Bothwell

2012

Molecules and Cells

149

111

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Members of the nuclear receptor superfamily function as transcription factors involved in innate and adaptive immunity as well as lipid metabolism. These highly conserved proteins participate in ligand-dependent or -independent regulatory mechanisms that affect gene expression. Peroxisome proliferator-activated receptors (PPARs), which include PPARα, PPARβ/δ, and PPARγ, are a group of nuclear receptor proteins that play diverse roles in cellular differentiation, development, and metabolism. Each PPAR subfamily is activated by different endogenous and synthetic ligands. Recent studies using specific ligand treatments and cell type-specific PPAR knockout mice have revealed important roles for these proteins in T-cell-related autoimmune diseases. Moreover, PPARs have been shown to regulate T-cell survival, activation, and CD4 + T helper cell differentiation into the Th1, Th2, Th17, and Treg lineages. Here, we review the studies that provide insight into the important regulatory roles of PPARs in T-cell activation, survival, proliferation, differentiation, and autoimmune disease.

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Section: Introductionmentioning

confidence: 99%

The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases

Choi¹,

Bothwell

2012

Molecules and Cells

149

111

View full text Add to dashboard Cite

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“…Human umbilical vein endothelial cells (HUVECs) were isolated from freshly derived umbilical cords by digestion with collagenase as described by Jaffe et al [24,25,27]. Umbilical cords were donated anonymously after informed consent according to national ethical legislation.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, the PPAR-γ agonist pioglitazone was shown to be effective in reducing inflammation in atherosclerosis disease models. For example, in these models, the levels of matrix metalloproteinase (MMP), TNFα and other cytokines were found to be reduced [23,24,25,26]. …”

Section: Introductionmentioning

confidence: 99%

T-Box20 Suppresses Oxidized Low-Density Lipoprotein-induced Human Vascular Endothelial Cell Injury by Upregulation of PPAR-γ

Shen

Zhu

Patel

et al. 2013

Cell Physiol Biochem

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Background: Atherosclerosis is a chronic inflammation disease which is initiated by endothelial cell injury Oxidized low-density lipoprotein (ox-LDL) is directly associated with chronic vascular inflammation. Many transcription factors take part in the initiation and progression of atherosclerosis. As a transcription factor mainly expressed in cardiovascular system, T-box20 (Tbx20) plays an important role in embryonic cardiovascular system development and homeostasis. However, the role of Tbx20 in endothelial cell injury and atherosclerosis is still not clear. We showed that Tbx20 might affect ox-LDL-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs). Methods and Results: First, Tbx20 expression was down regulated in the C57BL/6 mice with high-fat diet-induced artery injury, which was accompanied by elevated reactive oxygen species (ROS) generation and cell adhesion molecule expression. Second, ox-LDL led to concurrent decreased Tbx20 expression and increased levels of ROS and adhesion molecules in the HUVECs. Third, over-expression of Tbx20 by adenovirus reduced ox-LDL-induced HUVEC injury via attenuation of ROS generation and cell adhesion molecule expression. Fourth, knock down of Tbx20 by siRNA significantly increased adhesion molecule expression and decreased cell viability. Moreover, Tbx20 could directly regulate PPAR-γ expression, as shown by Tbx20 knock down and PPAR-γ inhibition, which significantly reversed Tbx20's HUVEC protection effect. Conclusions: These results indicate that misregulation of Tbx20 could reduce HUVEC tolerance of ox-LDL-induced cell injury, suggesting that Tbx20 might be a crucial regulator and potential therapeutic target for atherosclerosis.

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“…Peroxisome Proliferator-Activated Receptor (PPAR) is a subfamily of nuclear hormone receptors that regulate gene expression when activated [9]. The PPARγ isoform is expressed mostly in adipose tissue, and selective agonists, including thiazolidinedione derivatives such as rosiglitazone, pioglitazone, and troglitazone, are used clinically to treat DM [10,11].…”

Section: Introductionmentioning

confidence: 99%

Novel Partial Agonist of PPAR-Gamma for Treatment of Diabetic Neuropathy in Rats

Lima¹,

Trachez²,

Araujo³

et al. 2014

J Diabetes Metab 2013

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This work describes a novel ligand for peroxisome proliferator-activated receptor gamma (PPARgamma) and its hypoglycemic and analgesic activity in a murine model of diabetes-induced neuropathic pain. The molecular recognition of LASSBio-1772 by a PPARgamma binding domain showed that the compound is a partial agonist. Four weeks after male Wistar rats received a single intravenous injection of streptozotocin (STZ, 60 mg/kg), plasma glucose levels were increased from 92.5 ± 3.7 to 465.0 ± 21.6 mg/dL (P < 0.01) and serum insulin was reduced from 66.8 ± 7.8 to 25.5 ± 5.6 pmol/L (P<0.01). Diabetic animals were then, treated with either vehicle or LASSBio-1772 (50 mg/kg, i.p.) daily for 7 days. LASSBio-1772 significantly reduced blood glucose levels to 242.0 ± 55.1 mg/dL (P<0.05) and increased insulin levels to 58.7 ± 14.8 pmol/L (P<0.05), indicating the hypoglycemic activity of this compound. LASSBio-1772 also reduced the elevated triglyceride levels induced by STZ treatment from 74.1 ± 8.6 to 34.0 ± 6.3 mg/dL (P<0.01). LASSBio-1772 could reduce serum glucose levels via increased insulin levels and potentially improve insulin sensitivity. Neuropathy was detected after four weeks of STZ-induced diabetes, with reduced thermal heat withdrawal latency from 11.7 ± 0.1 to 7.1 ± 0.2 s (P<0.01) and paw withdrawal threshold from 37.5 ± 2.1 to 29.9 ± 1.1 g (P<0.05) indicating the establishment of hyperalgesia and allodynia. LASSBio-1772 treatment restored both measures to non-diabetic values (12.2 ± 0.4 s and 34.5 ± 1.5 g). In conclusion, treatment with LASSBio-1772, a partial PPARgamma agonist, decreased hyperglycemia and neuropathic pain induced by diabetes. PPARgamma stimulation by LASSBio-1772 could prevent inflammation and inhibit both peripheral and central sensitization.

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Structure and physiological functions of the human peroxisome proliferator-activated receptor γ

Cited by 107 publications

References 159 publications

The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases

The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases

T-Box20 Suppresses Oxidized Low-Density Lipoprotein-induced Human Vascular Endothelial Cell Injury by Upregulation of PPAR-γ

Novel Partial Agonist of PPAR-Gamma for Treatment of Diabetic Neuropathy in Rats

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