scholarly journals Phosphocaveolin-1 is a mechanotransducer that induces caveola biogenesis via Egr1 transcriptional regulation

2012 ◽  
Vol 199 (3) ◽  
pp. 425-435 ◽  
Author(s):  
Bharat Joshi ◽  
Michele Bastiani ◽  
Scott S. Strugnell ◽  
Cecile Boscher ◽  
Robert G. Parton ◽  
...  
Keyword(s):  
Carcinoma Cells ◽  
Caveolin 1 ◽  
Early Growth Response ◽  
Breast Carcinoma Cells ◽  
Transcriptional Inhibition ◽  
Kinase C ◽  
Tyrosine 14 ◽  
Regulatory Loop ◽  
Early Growth Response 1 ◽  
The Relationship

Caveolin-1 (Cav1) is an essential component of caveolae whose Src kinase-dependent phosphorylation on tyrosine 14 (Y14) is associated with regulation of focal adhesion dynamics. However, the relationship between these disparate functions remains to be elucidated. Caveola biogenesis requires expression of both Cav1 and cavin-1, but Cav1Y14 phosphorylation is dispensable. In this paper, we show that Cav1 tyrosine phosphorylation induces caveola biogenesis via actin-dependent mechanotransduction and inactivation of the Egr1 (early growth response-1) transcription factor, relieving inhibition of endogenous Cav1 and cavin-1 genes. Cav1 phosphorylation reduces Egr1 binding to Cav1 and cavin-1 promoters and stimulates their activity. In MDA-231 breast carcinoma cells that express elevated levels of Cav1 and caveolae, Egr1 regulated Cav1, and cavin-1 promoter activity was dependent on actin, Cav1, Src, and Rho-associated kinase as well as downstream protein kinase C (PKC) signaling. pCav1 is therefore a mechanotransducer that acts via PKC to relieve Egr1 transcriptional inhibition of Cav1 and cavin-1, defining a novel feedback regulatory loop to regulate caveola biogenesis.

scholarly journals Age-Related Increase in Caveolin-1 Expression Facilitates Cell-to-Cell Transmission of α-Synuclein in Neurons

2021 ◽  
Author(s):  
Tae-Young Ha ◽  
Yu Ree Choi ◽  
Hye Rin Noh ◽  
Seon-Heui Cha ◽  
Jae-Bong Kim ◽  
...  
Keyword(s):  
Risk Factor ◽  
Inclusion Bodies ◽  
Aging Process ◽  
Caveolin 1 ◽  
Age Related ◽  
Cell Transmission ◽  
Tyrosine 14 ◽  
The Relationship ◽  
The Brain ◽  
Related Increase

Abstract Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression. In the present study, we demonstrated that cav-1 expression in the brain increased with age, and considerably increased in the brain of A53T α-syn transgenic mice. Cav-1 overexpression facilitated the uptake of α-syn into neurons and formation of additional Lewy body-like inclusion bodies, phosphorylation of cav-1 at tyrosine 14 was found to be crucial for this process. This study demonstrates the relationship between age and α-syn spread and will facilitate our understanding of the molecular mechanism of the cell-to-cell transmission of α-syn.

scholarly journals Age-related increase in caveolin-1 expression facilitates cell-to-cell transmission of α-synuclein in neurons

2020 ◽  
Author(s):  
Tae-Young Ha ◽  
Yu Ree Choi ◽  
Hye Rin Noh ◽  
Seon-Heui Cha ◽  
Jae-Bong Kim ◽  
...  
Keyword(s):  
Lewy Body ◽  
Inclusion Bodies ◽  
Primary Neurons ◽  
Caveolin 1 ◽  
Age Related ◽  
Microfluidic Chamber ◽  
Cell Transmission ◽  
Tyrosine 14 ◽  
The Relationship ◽  
The Brain

Abstract Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression. In the present study, we explored the association between cav-1 and cell-to-cell transmission of α-syn.Methods: Using SH-SY5Y cells and primary neurons overexpressing WT and Y14A cav-1, we investigated the effect of cav-1 expression on the uptake of α-syn using a dual chamber system. Additionally, we investigated the effect of cav-1 expression on the formation of Lewy body-like inclusions using co-culture assay and microfluidic chamber assay.Results: We demonstrated that cav-1 expression in the brain increased with age, and considerably increased in the brain of A53T α-syn transgenic mice. Cav-1 overexpression facilitated the uptake of α-syn into neurons and formation of additional Lewy body-like inclusion bodies, phosphorylation of cav-1 at tyrosine 14 was found to be crucial for this process. Conclusions: This study demonstrates the relationship between age and α-syn spread and will facilitate our understanding of the molecular mechanism of the cell-to-cell transmission of α-syn.

CD24 expression and breast cancer stem cell phenotype

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11106-11106
Author(s):  
G. Rappa ◽  
F. Anzanello ◽  
A. Lorico
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Breast Carcinoma ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Carcinoma Cells ◽  
Cell Phenotype ◽  
Cell Cycle Distribution ◽  
Breast Carcinoma Cells ◽  
The Relationship

11106 Background: Several studies suggest the existence of breast cancer-initiating cells (BCIC), responsible for tumor development and progression. Initial reports that only the CD44+CD24−/low subpopulation contains BCIC have been challenged by subsequent studies. We examined the relationship between CD24 and biological properties of breast cancer cells. Methods: MA-11 breast carcinoma cells, originating from bone marrow micrometastases, are CD44+ and have an heterogeneous expression of CD24 (214,000/cell; range 0–1,120,000). We have previously reported that upon in vitro culture as mammospheres under stem cell-like conditions, MA-11 cells acquired increased tumorigenicity and a CD44+CD24−/low phenotype. We have now investigated the relationship between CD24 expression and tumorigenicity in the MA-11 model. Results: Upon passage of MA-11 mammospheres in adherent culture, cells rapidly re-expressed CD 24. The rapid increase in CD24 was consistent with antigen up-regulation, not selection of CD24−/low cells. Exposure of adherent MA-11 cells to imatinib for 72h resulted in a reversible decrease in CD24 from 214,000 to 15,800/cell. CD44+CD24−/low cells, sorted by flow cytometry, generated CD44+CD24high, and CD44+CD24highgenerated CD44+CD24−/low. Immediately after sorting, >90% CD44+CD24−/low cells were in G0/G1. After 24–48 h in culture, cell cycle distribution, growth rate and invasiveness of the sorted cell populations were equivalent. Upon injection and s.c. growth, CD24 expression of CD44+CD24−/low populations and clones increased from 10,000 to 220,000/cell. Similarly, CD44+CD24−/low clones derived from human MCF-7 breast carcinoma cells formed tumors containing >99% CD44+CD24high cells. The average number of CD24 per cell was equivalent for tumors formed upon injection of CD44+CD24−/low, CD44+CD24+, mammosphere-derived cells or parental adherent MA-11 cells. The tumorigenic potentials of sorted CD44+CD24−/low, CD44+CD24−/lowsub-populations and clones in nu/nu mice were equivalent. Conclusions: CD44+CD24−/low breast cancer cells are not associated with increased tumorigenicity; the high CD24 level of mouse xenografts derived from both CD44+CD24−/low and CD44+CD24hi breast cancer cells suggests an important role for CD24 in tumor growth. No significant financial relationships to disclose.

scholarly journals Age-Related Increase in Caveolin-1 Expression Facilitates Cell-To-Cell Transmission of α-Synuclein in Neurons

2020 ◽  
Author(s):  
Tae-Young Ha ◽  
Yu Ree Choi ◽  
Hye Rin Noh ◽  
Seon-Heui Cha ◽  
Jae-Bong Kim ◽  
...  
Keyword(s):  
Lewy Body ◽  
Inclusion Bodies ◽  
Primary Neurons ◽  
Caveolin 1 ◽  
Age Related ◽  
Microfluidic Chamber ◽  
Cell Transmission ◽  
Tyrosine 14 ◽  
The Relationship ◽  
The Brain

Abstract Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression. In the present study, we explored the association between cav-1 and cell-to-cell transmission of α-syn.Methods: Using SH-SY5Y cells and primary neurons overexpressing WT and Y14A cav-1, we investigated the effect of cav-1 expression on the uptake of α-syn using a dual chamber system. Additionally, we investigated the effect of cav-1 expression on the formation of Lewy body-like inclusions using co-culture assay and microfluidic chamber assay.Results: We demonstrated that cav-1 expression in the brain increased with age, and considerably increased in the brain of A53T α-syn transgenic mice. Cav-1 overexpression facilitated the uptake of α-syn into neurons and formation of additional Lewy body-like inclusion bodies, phosphorylation of cav-1 at tyrosine 14 was found to be crucial for this process. Conclusions: This study demonstrates the relationship between age and α-syn spread and will facilitate our understanding of the molecular mechanism of the cell-to-cell transmission of α-syn.

scholarly journals Early Growth Response 1 (Egr1) Is a Transcriptional Activator of NOX4 in Oxidative Stress of Diabetic Kidney Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Fang Hu ◽  
Meng Xue ◽  
Yang Li ◽  
Yi-Jie Jia ◽  
Zong-Ji Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Transcriptional Activator ◽  
Diabetic Mice ◽  
Diabetic Kidney ◽  
Early Growth Response ◽  
Nadph Oxidase 4 ◽  
Early Growth Response 1 ◽  
The Relationship

Background. NADPH oxidase 4 (NOX4) plays a major role in renal oxidative stress of diabetic kidney disease (DKD). NOX4 was significantly increased in Egr1-expressing fibroblasts, but the relationship between Egr1 and NOX4 in DKD is unclear. Methods. For the evaluation of the potential relationship between Egr1 and NOX4, both were detected in HFD/STZ-induced mice and HK-2 cells treated with TGF-β1. Then, changes in NOX4 expression were detected in HK-2 cells and mice with overexpression and knockdown of Egr1. The direct relationship between Egr1 and NOX4 was explored via chromatin immunoprecipitation (ChIP). Results. We found increased levels of Egr1, NOX4, and α-SMA in the kidney cortices of diabetic mice and in TGF-β1-treated HK-2 cells. Overexpression or silencing of Egr1 in HK-2 cells could upregulate or downregulate NOX4 and α-SMA. ChIP assays revealed that TGF-β1 induced Egr1 to bind to the NOX4 promoter. Finally, Egr1 overexpression or knockdown in diabetic mice could upregulate or downregulate the expression of NOX4 and ROS, and α-SMA was also changed. Conclusion. Our study provides strong evidence that Egr1 is a transcriptional activator of NOX4 in oxidative stress of DKD. Egr1 contributes to DKD by enhancing EMT, in part by targeting NOX4.

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