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Peroxisome proliferator activator receptor gamma AND leukemia

Jing-Yi Zhang, Min Wang, Rui-Ying Wang, Xiao Sun, Yu-Yang Du, Jing-Xue Ye, Gui-Bo Sun, Xiao-Bo Sun
Arsenic trioxide (ATO) is used as a therapeutic agent in the treatment of acute promyelocytic leukemia (APL). The therapeutic use of arsenic is limited due to its severe cardiovascular side effects. The cardio-protective effect of salvianolic acid A (Sal A) against ATO cardiotoxicity has been reported. However, the distinct role of the mitochondria in the cardio-protection of Sal A is not understood. The aim of this study was to determine whether Sal A preconditioning protects against ATO-induced heart injury by maintaining cardiac mitochondrial function and biogenesis...
2018: Frontiers in Pharmacology
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
December 2018: Redox Report: Communications in Free Radical Research
Jueqiong Wang, Liu Lu, Chung H Kok, Verity A Saunders, Jarrad M Goyne, Phuong Dang, Tamara M Leclercq, Timothy P Hughes, Deborah L White
Imatinib is actively transported by organic cation transporter-1 (OCT-1) influx transporter, and low OCT-1 activity in diagnostic chronic myeloid leukemia blood mononuclear cells is significantly associated with poor molecular response to imatinib. Herein we report that, in diagnostic chronic myeloid leukemia mononuclear cells and BCR-ABL1 + cell lines, peroxisome proliferator-activated receptor γ agonists (GW1929, rosiglitazone, pioglitazone) significantly decrease OCT-1 activity; conversely, peroxisome proliferator-activated receptor γ antagonists (GW9662, T0070907) increase OCT-1 activity...
May 2017: Haematologica
Emily R Finch, Diwakar B Tukaramrao, Laura L Goodfield, Michael D Quickel, Robert F Paulson, K Sandeep Prabhu
Supplementation with nontoxic doses of micronutrient selenium has been shown to alleviate chronic myelogenous leukemia (CML) via the elimination of leukemia stem cells (LSCs) in mice. This treatment provides a new and novel method for eliminating the LSCs that are otherwise not targeted by existing therapies. The antileukemic effect of selenium was dependent on the production of endogenous cyclopentenone prostaglandins (CyPGs), Δ-12 prostaglandin J2 (Δ12 -PGJ2 ), and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2 )...
March 30, 2017: Blood
Marie Saghaeian Jazi, Saeed Mohammadi, Yaghoub Yazdani, Sima Sedighi, Ali Memarian, Mehrdad Aghaei
OBJECTIVES: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA) as a recently emerged anti-neoplastic histone deacetylase (HDAC) inhibitor and pioglitazone (PGZ) as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ) agonist have been shown to induce apoptosis and cell cycle arrest in different studies...
July 2016: Iranian Journal of Basic Medical Sciences
B Yousefi, V Shafiei-Irannejad, A Azimi, N Samadi, N Zarghami
Peroxisome proliferator-activated receptor gamma (PPARγ) plays key roles in regulating cellular differentiation, proliferation and apoptosis pathways. As such, they are considered promising targets for anticancer drug development, especially for breast cancer, multiple myeloma and hematologic malignancies. Chronic myeloid leukemia (CML) is a myeloproliferative disorder arising from an oncogenic Bcr-Abl tyrosine kinase. Inhibitors of this oncogene by small molecules such as imatinib are effective only in 75% of the patient's population...
July 31, 2016: Cellular and Molecular Biology
Teresa Friedrich, Michaela Söhn, Tobias Gutting, Klaus-Peter Janssen, Hans-Michael Behrens, Christoph Röcken, Matthias P A Ebert, Elke Burgermeister
Full-length (FL) docking protein-1 (DOK1) is an adapter protein which inhibits growth factor and immune response pathways in normal tissues, but is frequently lost in human cancers. Small DOK1 variants remain in cells of solid tumors and leukemias, albeit, their functions are elusive. To assess the so far unknown role of DOK1 in colorectal cancer (CRC), we generated DOK1 mutants which mimic the domain structure and subcellular distribution of DOK1 protein variants in leukemia patients. We found that cytoplasmic DOK1 activated peroxisome-proliferator-activated-receptor-gamma (PPARγ) resulting in inhibition of the c-FOS promoter and cell proliferation, whereas nuclear DOK1 was inactive...
June 2016: EBioMedicine
Hardik Joshi, Kavita Marulkar, Vikram Gota, C S Ramaa
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that regulates the expression of many genes relevant to carcinogenesis. By analogy to selective estrogen receptor modulator for treatment of cancer, selective or partial PPARγ agonists are considered clinically important for chemotherapy of cancer. OBJECTIVE: In this study we have rationally modified the structure of existing p-coumaric acid and ferulic acid, which would selectively activate PPARγ and exert their anti-proliferative effect at lower dose as compared to natural phytoconstituents...
2017: Anti-cancer Agents in Medicinal Chemistry
Xiao Cong Zeng, Lang Li, Hong Wen, Qi Bi
The aim of the present study was to investigate the effects of microRNA (miR)-128 inhibition on the targeted activation of peroxisome proliferator-activated receptor gamma (PPARG) and on cardiomyocyte apoptosis induced by myocardial ischemia/reperfusion (I/R) injury. In vitro, the expression of PPARG was detected by reverse transcription-quantitative polymerase chain reaction and western blotting in neonatal rat ventricular myocytes (NRVMs) and HEK293 cells transfected with the mimics or inhibitors of miR‑128 or control RNA...
July 2016: Molecular Medicine Reports
Chengming Sun, Guili Zhang, Shuping Luan, Caifu Luan, Huiyuan Shao, Fei Dong, Xuena Liu
Evodiamine, a quinolone alkaloid, is one of the major bioactive compounds of Evodia rutaecarpa Bentham (Rutaceae). It exhibits excellent biological activities, especially the anticancer activity. This study aims to investigate the effect of evodiamine on the proliferation of leukemia cell line K562 and to explore the underlying mechanism. The effect of evodiamine on K562 cells proliferation was analyzed by trypan blue dye exclusion assay and MTT assay. The expression levels of peroxisome proliferators-activated receptor gamma (PPARγ), cyclin D1, and p21 were detected by western blot assay...
August 2016: Journal of Receptor and Signal Transduction Research
Jie Gao, Jiong Yan, Meishu Xu, Songrong Ren, Wen Xie
The constitutive androstane receptor (CAR) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α) are master regulators of drug metabolism and gluconeogenesis, respectively. In supporting the cross talk between drug metabolism and energy metabolism, activation of CAR has been shown to suppress hepatic gluconeogenesis and ameliorate hyperglycemia in vivo, but the underlying molecular mechanism remains elusive. In this study, we demonstrated that CAR suppressed hepatic gluconeogenic gene expression through posttranslational regulation of the subcellular localization and degradation of PGC1α...
November 2015: Molecular Endocrinology
Stéphane Prost, Francis Relouzat, Marc Spentchian, Yasmine Ouzegdouh, Joseph Saliba, Gérald Massonnet, Jean-Paul Beressi, Els Verhoeyen, Victoria Raggueneau, Benjamin Maneglier, Sylvie Castaigne, Christine Chomienne, Stany Chrétien, Philippe Rousselot, Philippe Leboulch
Whether cancer is maintained by a small number of stem cells or is composed of proliferating cells with approximate phenotypic equivalency is a central question in cancer biology. In the stem cell hypothesis, relapse after treatment may occur by failure to eradicate cancer stem cells. Chronic myeloid leukaemia (CML) is quintessential to this hypothesis. CML is a myeloproliferative disorder that results from dysregulated tyrosine kinase activity of the fusion oncoprotein BCR-ABL. During the chronic phase, this sole genetic abnormality (chromosomal translocation Ph(+): t(9;22)(q34;q11)) at the stem cell level causes increased proliferation of myeloid cells without loss of their capacity to differentiate...
September 17, 2015: Nature
Rom Keshet, Zina Bryansker Kraitshtein, Matan Shanzer, Julia Adler, Nina Reuven, Yosef Shaul
Adipocyte differentiation, or adipogenesis, is a complex and highly regulated process. A recent proteomic analysis has predicted that the nonreceptor tyrosine kinase Abelson murine leukemia viral oncogene (c-Abl) is a putative key regulator of adipogenesis, but the underlying mechanism remained obscure. We found that c-Abl was activated during the early phase of mouse 3T3-L1 preadipocyte differentiation. Moreover, c-Abl activity was essential and its inhibition blocked differentiation to mature adipocytes. c-Abl directly controlled the expression and activity of the master adipogenic regulator peroxisome proliferator-activator receptor gamma 2 (PPARγ2)...
November 18, 2014: Proceedings of the National Academy of Sciences of the United States of America
Hiroyuki Nobusue, Nobuyuki Onishi, Takatsune Shimizu, Eiji Sugihara, Yoshinao Oki, Yuko Sumikawa, Tatsuyuki Chiyoda, Koichi Akashi, Hideyuki Saya, Koichiro Kano
Cellular differentiation is regulated through activation and repression of defined transcription factors. A hallmark of differentiation is a pronounced change in cell shape, which is determined by dynamics of the actin cytoskeleton. Here we show that regulation of the transcriptional coactivator MKL1 (megakaryoblastic leukemia 1) by actin cytoskeleton dynamics drives adipocyte differentiation mediated by peroxisome proliferator-activated receptor γ (PPARγ), a master transcriptional regulator of adipogenesis...
2014: Nature Communications
Maryam Peymani, Ali Ghoochani, Kamran Ghaedi, Fereshteh Karamali, Khadijeh Karbalaie, Abbas Kiani-Esfahani, Farzaneh Rabiee, Mohammad Hossein Nasr-Esfahani, Hossein Baharvand
The aim of this study was to evaluate the influence of peroxisome proliferator-activated receptor γ (PPARγ) on self-renewal of mouse embryonic stem cells (mESCs) in the presence and absence of leukemia inhibitory factor (LIF). We demonstrated that in the presence of LIF, the activation of PPARγ by Rosiglitazone led to an increased proliferation of mESCs whereas PPARγ antagonist (GW9662) reversed this effect. Additionally, upon PPARγ activation, LIF increased PPARγ expression and resulted in the degradation of suppressor of cytokine signaling 3 (SOCS3), an important negative regulator of LIF/signal transducers and activators of transcription 3 (STAT3)-pathway...
April 2013: European Journal of Cell Biology
L Zang, B Xue, Z Lu, X Li, G Yang, Q Guo, J Ba, X Zou, J Dou, J Lu, C Pan, Y Mu
Leukemia related protein 16 (LRP16) was first cloned from acute myeloid leukemia cells in our laboratory. In the present study, we sought to investigate the role of LRP16 in insulin action and sensitivity, using LRP16-depleted and -overexpressing 3T3-L1 cells. LRP16 silencing resulted in a reduction of the expression and secretion of tumor necrosis factor-alpha (TNF-α) and a concomitant increase in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ). Moreover, LRP16 depletion promoted insulin-induced glucose uptake and adipocyte differentiation of 3T3-L1 cells...
May 2013: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Omar M Khan, Murali K Akula, Kristina Skålen, Christin Karlsson, Marcus Ståhlman, Stephen G Young, Jan Borén, Martin O Bergo
BACKGROUND: Statins have antiinflammatory and antiatherogenic effects that have been attributed to inhibition of RHO protein geranylgeranylation in inflammatory cells. The activity of protein geranylgeranyltransferase type I (GGTase-I) is widely believed to promote membrane association and activation of RHO family proteins. However, we recently showed that knockout of GGTase-I in macrophages activates RHO proteins and proinflammatory signaling pathways, leading to increased cytokine production and rheumatoid arthritis...
February 19, 2013: Circulation
Lihui Wang, Athina Giannoudis, Gemma Austin, Richard E Clark
Low pretreatment expression of the imatinib uptake transporter human organic cation transporter 1 (hOCT1) is associated with inferior complete cytogenetic response rates, progression-free survival, and overall survival in imatinib-treated chronic myeloid leukemia (CML). Upregulation of hOCT1 can therefore increase the uptake of imatinib. The hOCT1 gene is transactivated by hepatocyte nuclear factor 4α in human liver, and peroxisome proliferator-activated receptors (PPAR) α and γ activation increases OCT1 expression in mouse hepatocytes...
October 2012: Experimental Hematology
Yue-min Nan, Fang Han, Ling-bo Kong, Ya Li, Rong-qi Wang, Su-xian Zhao
OBJECTIVE: To elucidate the effect of targeted gene modulation of peroxisome proliferator activated receptor gamma (PPARg) on hepatocellular apoptosis in nutritional fibrotic steatohepatitis in mice. C57BL/6J mice were fed with high fat, methionine-choline deficient (MCD) diet for 8 weeks to induce fibrotic steatohepatitis. Mice fed the MCD diet were treated with adenovirus carrying PPARg (Ad-PPARg), adenovirus-beta-galactosidase (Ad-LacZ), Ad-PPARg plus PPARg agonist rosiglitazone, or PPARg antagonist 2-chloro-5-nitro- benzanilide (GW9662), respectively...
July 2011: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Jun-Bean Park, Baek-Kyung Kim, Yoo-Wook Kwon, Dominik N Muller, Hyun-Chae Lee, Seock-Won Youn, Young-Eun Choi, Sae-Won Lee, Han-Mo Yang, Hyun-Jai Cho, Kyung Woo Park, Hyo-Soo Kim
The role and underlying mechanisms of rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist, on myocardial infarction are poorly understood. We investigated the effects of this PPAR-γ agonist on the expression of tissue factor (TF), a primary molecule for thrombosis, and elucidated its underlying mechanisms. The PPAR-γ agonist inhibited TF expression in response to TNF-α in human umbilical vein endothelial cells, human monocytic leukemia cell line, and human umbilical arterial smooth muscle cells...
2011: PloS One
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