Phosphatase and Tensin Homolog Deleted on Chromosome 10 Suppression Is an Important Process in Peroxisome Proliferator-Activated Receptor-γ Signaling in Adipocytes and Myotubes

2007 ◽  
Vol 71 (6) ◽  
pp. 1554-1562 ◽  
Author(s):  
Ki Young Kim ◽  
Hyun Sill Cho ◽  
Won Hoon Jung ◽  
Sung Soo Kim ◽  
Hyae Gyeong Cheon
Author(s):  
Annu Makker ◽  
Madhu Mati Goel ◽  
Kumari Manu ◽  
Renu Makker

Background: Balance between endometrial cell proliferation and apoptosis is crucial for successful embryo implantation. PTEN (phosphatase and tensin homolog deleted on chromosome 10), a pro-apoptotic factor, is proposed to be one of the signaling proteins through which estrogen and progesterone act to affect cellular homeostasis. Although reports in literature have suggested role of PTEN in regulating endometrial cell proliferation and apoptosis during window of implantation, its involvement in women with unexplained infertility is not clear. In the present study, we examined expression, cellular distribution and activation status of PTEN, cell proliferation, and apoptosis in midsecretory endometrium from women with unexplained infertility as compared to fertile controls.Methods: Endometrial biopsies from infertile (n=11) and fertile women (n=22) were used for immunohistochemical evaluation of PTEN, phospho-PTEN and Ki67. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay was performed for detection of apoptotic cells.Results: Biopsies from infertile women as compared to fertile controls demonstrated statistically significant: i) decrease in nuclear PTEN (P < 0.001), increase in nuclear phospho-PTEN (P < 0.05), increase in nuclear and cytoplasmic phospho-PTEN/PTEN ratio (P < 0.001 and P < 0.05 respectively) in endometrial stroma, ii) increase in cytoplasmic phospho-PTEN (P < 0.001) and phospho-PTEN/PTEN ratio (P < 0.05) in glandular epithelium (GE), iii) increase in Ki67 labeling in GE (P < 0.01) and stroma (P < 0.05) and, iv) decrease in (P < 0.001) apoptosis.Conclusions: Altered PTEN expression and associated modulation in cellular homeostasis during the implantation window might contribute to mechanism underlying unexplained infertility.


Reproduction ◽  
2012 ◽  
Vol 144 (3) ◽  
pp. 373-383 ◽  
Author(s):  
Isha Sharma ◽  
Dheer Singh

Conjugated linoleic acid (CLA) has drawn much interest in last two decades in the area ranging from anticancer activity to obesity. A number of research papers have been published recently with regard to CLA's additional biological functions as reproductive benefits. However, not much is known how this mixture of isomeric compounds mediates its beneficial effects particularly on fertility. In this study, we demonstrated the cross talk between downstream signaling of CLA and important hormone regulators of endocrine system, i.e. FSH and IGF1, on buffalo granulosa cell function (proliferation and steroidogenesis). Experiments were performed in primary serum-free buffalo granulosa cell culture, where cells were incubated with CLA in combination with FSH (25 ng/ml) and IGF1 (50 ng/ml). Results showed that 10 μM CLA inhibits FSH- and IGF1-induced granulosa cell proliferation; aromatase,GATA4, andIGF1mRNA; and estradiol-17β production. Western blot analysis of total cell lysates revealed that CLA intervenes the IGF1 signaling by decreasing p-Akt. In addition, CLA was found to upregulate peroxisome proliferator-activated receptor-gamma (PPARG) and phosphatase and tensin homolog (PTEN) level in granulosa cells. Further study using PPARG- and PTEN-specific inhibitors supports the potential role of CLA in granulosa cell proliferation and steroidogenesis involving PPARG, PTEN, and PI3K/Akt pathway.


2010 ◽  
Vol 28 (36) ◽  
pp. e767-e768 ◽  
Author(s):  
Mrinal M. Patnaik ◽  
Sania S. Raza ◽  
Sherezade Khambatta ◽  
Peter P. Stanich ◽  
Matthew P. Goetz

Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6702-6713 ◽  
Author(s):  
Yitang Li ◽  
Amit Prasad ◽  
Yonghui Jia ◽  
Saurabh Ghosh Roy ◽  
Fabien Loison ◽  
...  

Abstract The clinical outcome of granulocyte transfusion therapy is often hampered by short ex vivo shelf life, inefficiency of recruitment to sites of inflammation, and poor pathogen-killing capability of transplanted neutrophils. Here, using a recently developed mouse granulocyte transfusion model, we revealed that the efficacy of granulocyte transfusion can be significantly increased by elevating intracellular phosphatidylinositol (3,4,5)-trisphosphate signaling with a specific phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitor SF1670. Neutrophils treated with SF1670 were much sensitive to chemoattractant stimulation. Neutrophil functions, such as phagocytosis, oxidative burst, polarization, and chemotaxis, were augmented after SF1670 treatment. The recruitment of SF1670-pretreated transfused neutrophils to the inflamed peritoneal cavity and lungs was significantly elevated. In addition, transfusion with SF1670-treated neutrophils led to augmented bacteria-killing capability (decreased bacterial burden) in neutropenic recipient mice in both peritonitis and bacterial pneumonia. Consequently, this alleviated the severity of and decreased the mortality of neutropenia-related pneumonia. Together, these observations demonstrate that the innate immune responses can be enhanced and the severity of neutropenia-related infection can be alleviated by augmenting phosphatidylinositol (3,4,5)-trisphosphate in transfused neutrophils with PTEN inhibitor SF1670, providing a therapeutic strategy for improving the efficacy of granulocyte transfusion.


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