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CHPG's role in regulating apoptosis in heat-stressed microglia through endoplasmic reticulum stress: A new
Yan-Xuan He1, Zhi-Qiang Zhang2, Xin-Xin Zheng2
1Wenzhou Medical University, Wenzhou 325006, China.
Objective:
This study aims to explore the influence of microglia-mediated endoplasmic reticulum (ER) stress on cell apoptosis during heat stroke. Understanding this is important as it may help develop new therapies for heat-induced cellular damage and protect glial cells and brain health.
Methods:
BV-2 cells were used as a cell model for this study. The negative control group was kept at 37°C throughout the experiment. Cells in the experimental group were pretreated with 1 mM CHPG (a selective mGluR5 agonist) for 0.5 hours, followed by heat shock (HS) for 0.5 hours at 40°C and then further cultivation at 37°C for 12 hours. The positive control cells underwent same condition except for drug pretreatment. Several assays were used including CCK8 assay for cell viability, flow cytometry for cell apoptosis index, immunofluorescence for the expression of GRP78, CHOP, and Caspase-12, as well as Western blotting for detecting the protein expression level of GRP78, CHOP, and Caspase-12.
Results:
Heat shock induced a significant release of endoplasmic reticulum-related proteins and increased the expression levels of GRP78, CHOP, and Caspase-12 in BV-2 cells. CHPG was found to inhibit endoplasmic reticulum stress and cell apoptosis.
Conclusion:
CHPG may primarily participate in heat shock by mediating endoplasmic reticulum stress and affecting microglia apoptosis.
Insights
Heat shock triggers endoplasmic reticulum (ER) stress and cell death in microglia. A drug called CHPG was found to reduce this ER stress and protect cells from heat-induced apoptosis.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Heat stroke causes cellular damage, particularly to brain cells.
- Microglia, the brain's immune cells, are susceptible to heat-induced stress.
- Endoplasmic reticulum (ER) stress is implicated in various cellular injury pathways.
Purpose of the Study:
- To investigate the role of microglia-mediated ER stress in heat stroke-induced apoptosis.
- To explore the potential protective effects of CHPG on heat-stressed microglia.
- To understand the molecular mechanisms linking ER stress, microglia, and heat stroke.
Main Methods:
- Utilized BV-2 microglial cells as a model system.
- Applied heat shock (HS) at 40°C to induce cellular stress.
- Treated cells with CHPG, a selective mGluR5 agonist, to assess its protective effects.
- Quantified cell viability (CCK8 assay), apoptosis (flow cytometry), and expression of ER stress markers (GRP78, CHOP, Caspase-12) via immunofluorescence and Western blotting.
Main Results:
- Heat shock significantly increased the release of ER-related proteins and upregulated GRP78, CHOP, and Caspase-12 expression in BV-2 cells.
- CHPG treatment effectively inhibited heat shock-induced ER stress.
- CHPG demonstrated a significant reduction in microglial apoptosis following heat exposure.
Conclusions:
- Microglia-mediated ER stress plays a crucial role in the cellular response to heat stroke.
- CHPG exhibits a protective effect against heat-induced apoptosis in microglia, likely by mitigating ER stress.
- Targeting ER stress pathways in microglia may offer a therapeutic strategy for managing heat stroke-related brain injury.
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