The goal of this project is to identify molecules that prevent apoptosis in pancreatic beta cells that is induced by a combination of cytokines, namely Interferon-gamma, Interleukin 1-beta and tumor necrosis factor-alpha. ..more
Depositor Specified Assays
Show more |
| AID | Name | Type | Comment |
|---|---|---|---|
| 435005 | Luminescence Cell-Based Primary HTS to Identify Inhibitors of Beta Cell Apoptosis. | screening | Primary HTS |
| 488844 | Detect Cellular ATP-levels in INS-1E Cells Measured in Cell-Based System Using Plate Reader - 2061-01_Inhibitor_Dose_DryPowder_Activity | confirmatory | Retest at dose for primary HTS hits |
| 488910 | Detect Cellular ATP-levels in INS-1E Cells Measured in Cell-Based System Using Plate Reader - 2061-01_Inhibitor_SinglePoint_HTS_Activity | screening | Primary HTS on additional library compounds |
| 488848 | Apoptosis Measured in Cell-Based System Using Plate Reader - 2061-02_Inhibitor_Dose_DryPowder_Activity | confirmatory | Testing compounds for reduction of caspase activity in INS-1E cells challenged with cytokine and glucose |
| 488936 | Apoptosis Measured in Cell-Based System Using Plate Reader - 2061-02_Inhibitor_Dose_DryPowder_Activity_Set2 | confirmatory | Testing additional round compounds for reduction of caspase activity in INS-1E cells challenged with cytokine and glucose |
| 488931 | Apoptosis Measured in Cell-Based System Using Plate Reader - 2061-03_Inhibitor_Dose_DryPowder_Activity | confirmatory | Testing compounds to assess mitochondrial depolarization in INS-1E cells challenged with cytokine and glucose |
| 488867 | Apoptosis Measured in Cell-Based System Using Plate Reader - 2061-03_Inhibitor_Dose_DryPowder_Activity_Set2 | confirmatory | Testing additional round compounds to assess mitochondrial depolarization in INS-1E cells challenged with cytokine and glucose |
| 488866 | Nitrite Measured in Cell-Based System Using Plate Reader - 2061-04_Inhibitor_Dose_DryPowder_Activity | confirmatory | Testing compounds for effect on nitrite production as a measure of apoptosis |
| 488868 | Nitrite Measured in Cell-Based System Using Plate Reader - 2061-04_Inhibitor_Dose_DryPowder_Activity_Set2 | confirmatory | Testing additional round compounds for effect on nitrite production as a measure of apoptosis |
| 488870 | Nitrite Measured in Cell-Based System Using Plate Reader - 2061-04_Inhibitor_Dose_DryPowder_Activity_Set3 | confirmatory | Testing additional round compounds for effect on nitrite production as a measure of apoptosis |
| 488959 | Glucose-induced Insulin secretion ELISA Measured in Cell-Based System Using Plate Reader - 2061-05_Inhibitor_Dose_DryPowder_Activity | confirmatory | Testing compounds for effect on glucose-induced insulin secretion in INS-1E cells |
| 488864 | ATP-based Luminescence in the Absence of Cytokines Measured in Cell-Based System Using Plate Reader - 2061-06_Inhibitor_Dose_DryPowder_Activity | confirmatory | Testing compounds for effect on viability in INS-1E cells in the absence of cytokine |
| 488945 | Primary Beta Cell Apoptosis assay Measured in Cell-Based System Using Plate Reader - 2061-07_Inhibitor_Dose_DryPowder_Activity_Set2 | confirmatory | Testing compounds for reduction of caspase activity in primary human islet cells challenged with cytokine and glucose |
| 488951 | Primary beta islet insulin ELISA Measured in Cell-Based System Using Plate Reader - 2061-09_Inhibitor_Dose_DryPowder_Activity | confirmatory | Testing compounds for effect on glucose-induced insulin secretion in primary human islet cells |
| 449756 | Luminescence Cell-Based Dose Retest to Confirm Inhibitors of Beta Cell Apoptosis | confirmatory | |
| 463206 | Luminescence Cell-Based Counter Screen to Identify Inhibitors of Cytokine Induced Apoptosis | confirmatory | |
| 463229 | ATP-based Luminescence in the Absence of Cytokines Measured in Cell-Based System Using Plate Reader - 2061-06_Inhibitor_Dose_CherryPick | confirmatory | |
| 652090 | On Hold | ||
| 652132 | On Hold | ||
| 652171 | On Hold | ||
| 652206 | On Hold | ||
| 652234 | On Hold | ||
| 652237 | On Hold | ||
| 652238 | On Hold | ||
| 652240 | On Hold |
Description:
Primary Collaborators:
Bridget Wagner,Broad Institute,Cambridge, MA,bwagner@broadinstitute.org,617-714-7363
Danny Chou,Broad Institute,Cambridge, MA,dchou@broadinstitute.org
Project Goal:
The goal of this project is to identify molecules that prevent apoptosis in pancreatic beta cells that is induced by a combination of cytokines, namely Interferon-gamma, Interleukin 1-beta and tumor necrosis factor-alpha.
Keywords:
Diabetes, apoptosis, cytokine, beta cells, insulin
Biological Relevance:
Type 1 diabetes is caused by autoimmune destruction of insulin-producing beta cells in the pancreas. Human beta-cell apoptosis in this process involves a complex set of signaling cascades initiated by interleukin-1b (IL-1b), interferon-g (IFN-g), and tumor necrosis factor-a (TNF-a). IL-1b and TNF-a induce NFkB expression, while downstream activation of gene expression is thought to occur through nitric oxide (NO) signaling, which both increases the endoplasmic reticulum stress-response pathway and decreases beta-cell function. These effects of cytokines are beta cell-specific, and we aim to find small-molecule suppressors that would have little to no effect on other cell types in the pancreas.
Small molecules that increase beta-cell survival in the presence of cytokines could be of potential clinical benefit to early-stage type 1 diabetic patients. A number of studies have described small molecules with protective effects in the presence of cytokines; most of these were discovered because of their antioxidant or anti-inflammatory effects. Further, small-molecule inhibition of histone deacetylases (HDAC) with suberoylanilide hydroxamic acid (SAHA) or trichostatin A (TSA) can prevent cytokine-induced beta-cell death, presumably by decreasing NFkB transactivation. Therefore, multiple mechanisms may serve to protect beta cells from cytokine-induced apoptosis.
Bridget Wagner,Broad Institute,Cambridge, MA,bwagner@broadinstitute.org,617-714-7363
Danny Chou,Broad Institute,Cambridge, MA,dchou@broadinstitute.org
Project Goal:
The goal of this project is to identify molecules that prevent apoptosis in pancreatic beta cells that is induced by a combination of cytokines, namely Interferon-gamma, Interleukin 1-beta and tumor necrosis factor-alpha.
Keywords:
Diabetes, apoptosis, cytokine, beta cells, insulin
Biological Relevance:
Type 1 diabetes is caused by autoimmune destruction of insulin-producing beta cells in the pancreas. Human beta-cell apoptosis in this process involves a complex set of signaling cascades initiated by interleukin-1b (IL-1b), interferon-g (IFN-g), and tumor necrosis factor-a (TNF-a). IL-1b and TNF-a induce NFkB expression, while downstream activation of gene expression is thought to occur through nitric oxide (NO) signaling, which both increases the endoplasmic reticulum stress-response pathway and decreases beta-cell function. These effects of cytokines are beta cell-specific, and we aim to find small-molecule suppressors that would have little to no effect on other cell types in the pancreas.
Small molecules that increase beta-cell survival in the presence of cytokines could be of potential clinical benefit to early-stage type 1 diabetic patients. A number of studies have described small molecules with protective effects in the presence of cytokines; most of these were discovered because of their antioxidant or anti-inflammatory effects. Further, small-molecule inhibition of histone deacetylases (HDAC) with suberoylanilide hydroxamic acid (SAHA) or trichostatin A (TSA) can prevent cytokine-induced beta-cell death, presumably by decreasing NFkB transactivation. Therefore, multiple mechanisms may serve to protect beta cells from cytokine-induced apoptosis.
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome |
Additional Information
Grant Number: DP2 DK083048
Data Table (Concise)
PageFrom: