Expression of Selected Apoptosis Related Genes, MIF, IGIF and TNF.ALPHA., during Retinoic Acid-Induced Neural Differentiation in Murine Embryonic Stem Cells.

Sarkar, Sagartirtha; Sharma, Raghubir P.

doi:10.1247/csf.27.99

Cited by 21 publications

(16 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the proteins we confidently identified and quantified with global proteomics methodologies, many had been reported previously (4,(25)(26)(27), providing a degree of assurance regarding the approach. For example, following noggin treatment, the neural cell-specific proteins tubulin ␤-III and the CRMP isoforms were identified and in the case of CRMP4 found to be increased as expected (4,28,29).…”

Section: Discussionmentioning

confidence: 77%

Coupled Global and Targeted Proteomics of Human Embryonic Stem Cells during Induced Differentiation

Yocum

Gratsch

Leff

et al. 2008

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Elucidating the complex combinations of growth factors and signaling molecules that maintain pluripotency or, alternatively, promote the controlled differentiation of human embryonic stem cells (hESCs) has important implications for the fundamental understanding of human development, devising cell replacement therapies, and cancer cell biology. hESCs are commonly grown on irradiated mouse embryonic fibroblasts (MEFs) or in conditioned medium from MEFs. These culture conditions interfere with many experimental conclusions and limit the ability to perform conclusive proteomics studies. The current investigation avoided the use of MEFs or MEF-conditioned medium for hESC culture, allowing global proteomics analysis without these confounding conditions, and elucidated neural cell-specific signaling pathways involved in noggin-induced hESC differentiation. Based on these analyses, we propose the following early markers of hESC neural differentiation: collapsin response mediator proteins 2 and 4 and the nuclear autoantigenic sperm protein as a marker of pluripotent hESCs. We then developed a directed mass spectrometry assay using multiple reaction monitoring (MRM) to identify and quantify these markers and in addition the epidermal ectoderm marker cytokeratin-8. Analysis of global proteomics, quantitative RT-PCR, and MRM data led to testing the isoform interference hypothesis where redundant peptides dilute quantification measurements of homologous proteins. These results show that targeted MRM analysis on nonredundant peptides provides more exact quantification of homologous proteins. This study describes the facile transition from discovery proteomics to targeted MRM analysis and allowed us to identify and verify several potential biomarkers for hESCs during noggin-induced neural and BMP4-induced epidermal ectoderm differentiation. Molecular & Cellular Proteomics 7:750 -767, 2008.Human embryonic stem cells (hESCs) 1 are perhaps the most promising source of cells for regenerative medicine and treatment of disease. Despite extensive research aimed at elucidating and controlling the processes of self-renewal and lineage-specific differentiation, much remains to be learned regarding the basic cell biology of hESCs before their clinical potential can be realized. Our current knowledge regarding the complex regulation of lineage segregation during development arises primarily from in vivo investigations in invertebrate and mouse. Furthermore manipulation of the signaling pathways initiating and controlling lineage differentiation during development, including the role of bone morphogenic proteins (BMPs), has been expedited by in vitro studies of mouse embryonic stem cells (mESCs). Only recently has considerable research commenced on hESCs.BMPs were originally characterized based on their ability to induce cartilage and bone formation. They are now known to be multifunctional regulators of development, including many non-osteogenic processes (1). There are as many as 30 different BMP family members classified according to...

show abstract

Section: Discussionmentioning

confidence: 77%

Coupled Global and Targeted Proteomics of Human Embryonic Stem Cells during Induced Differentiation

Yocum

Gratsch

Leff

et al. 2008

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

show abstract

“…However, TNF-␣ is expressed not only in dying neurons but also in surviving neurons (Barker et al, 2001) and the function of endogenous TNF-␣ in surviving neurons has not been clarified. Other groups have reported endogenous TNF-␣ in other types of neurons, but could not show significant death of neurons that express TNF-␣ (Renauld and Spengler, 2002;Sarkar and Sharma, 2002;Klassen et al, 2003). This study shows a mechanism in which endogenous TNF-␣ can promote neural cell survival, rather than cell killing, but by signaling through TNFR2.…”

Section: Discussionmentioning

confidence: 45%

“…Because Akt is involved in the signaling for promotion of neural cell survival (Song et al, 2005), Figure 5, A and B, suggests that TNF-␣ signaling from TNFR2 could contribute to promotion of neural cell survival through Akt activation. Consistent with this possibility, signaling from TNFR2 can promote survival of several types of neurons (Renauld and Spengler, 2002;Sarkar and Sharma, 2002;Klassen et al, 2003).…”

Section: Induction Of Tnf-␣ By Ngf Contributes To Ngf-dependent Survimentioning

confidence: 63%

“…Several groups have independently reported the synthesis of TNF-␣ in neural cells, including multipotential neural stem cells and differentiated hippocampal neurons (Barker et al, 2001;Sarkar and Sharma, 2002;Renauld and Spengler, 2002;Klassen et al, 2003). Endogenous TNF-␣ in NGF-dependent neurons is reported to contribute to induction of neural cell death through TNFR1 after withdrawal of NGF (Barker et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor Necrosis Factor α Regulates Responses to Nerve Growth Factor, Promoting Neural Cell Survival but Suppressing Differentiation of Neuroblastoma Cells

Takei

Laskey

2008

MBoC

View full text Add to dashboard Cite

“…MIF has also been shown to be involved in TNF -mediated cell death. For example, apoptotic mature neutrophils were shown to release MIF upon stimulation with TNF [50], and that retinoic acid-mediated apoptosis has been shown to involve the expression of apoptosis related genes like MIF, IGIF and TNF [51]. In order for TNF -mediated cell death to occur, TNF has to bind to two different cell surface receptors, the TNF receptor type I (TNFRI) and the TNF receptor type II (TNFRII) [52].…”

Section: Subcellular Protein Identificationmentioning

confidence: 99%

Impact of p21 Knockout on Topotecan-Induced Stress Responses in Human Colon Carcinoma Cells: A Proteomic Analysis

Lee¹,

Daoud²

2009

TOPROTJ

View full text Add to dashboard Cite

There are few reports describing the role of p21-dependent protein repression in cell death. To identify such cell death-associated proteins and to shed the light into the molecular mechanisms by which p21 is responding to pharmacological stress, we used a subcellular proteomic approach for the analysis of protein expression profiles of fractionated nuclei, mitochondria, and cytosols of isogenic p21 null (p21-/-) and wild-type human HCT-116 cells following treatment with sublethal doses (1μM) of the topoisomerase I inhibitor, topotecan (TPT). In total, 174 unique deregulated proteins were identified in HCT-116 cells following treatment with TPT, whereas only 146 proteins were identified in p21-/-cells. They contributed to multiple functional activities of stress signaling pathways, and that p21-/-cells are accelerated to be more responsive to topotecan-induced cell death due to the following: 1) down regulation of proteins involved in the transcriptional and replication machinery of cells like DNA (cytosine-5)-methyltransferase 1, Matrin 3, DNA replication licensing factor MCM4, heterogeneous nuclear ribonucleoprotein Q, poly(Rc)-binding protein 1 and splicing factor arginine serine rich 7; 2) the activation of a caspase-independent apoptosis by the upregulation of the Bcl2 inhibitor of transcription (Bit1) protein; and 3) the activation of TNF signaling by the upregulation of macrophage immigration inhibitory factor (MIF), and 26S proteosome non-ATPase regulatory subunit 2 (TRAP2) proteins. We suggest that the upregulation of these proteins are contributing factors to the molecular mechanisms of topotecan-induced cell death in p21-/-cells; and that the data present an opportunity for developing new therapeutic approaches for selective targeting of p21-signaling pathways.

show abstract

Expression of Selected Apoptosis Related Genes, MIF, IGIF and TNF.ALPHA., during Retinoic Acid-Induced Neural Differentiation in Murine Embryonic Stem Cells.

Cited by 21 publications

References 42 publications

Coupled Global and Targeted Proteomics of Human Embryonic Stem Cells during Induced Differentiation

Coupled Global and Targeted Proteomics of Human Embryonic Stem Cells during Induced Differentiation

Tumor Necrosis Factor α Regulates Responses to Nerve Growth Factor, Promoting Neural Cell Survival but Suppressing Differentiation of Neuroblastoma Cells

Impact of p21 Knockout on Topotecan-Induced Stress Responses in Human Colon Carcinoma Cells: A Proteomic Analysis

Contact Info

Product

Resources

About