negative regulation of myeloid cell apoptotic process

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate, or extent of a myeloid cell apoptotic process. [GOC:add, GOC:mtg_apoptosis]

Negative regulation of myeloid cell apoptotic process is a critical cellular mechanism that prevents premature or inappropriate death of myeloid cells. These cells are essential for immune defense, inflammation, and tissue repair. Myeloid cells encompass a diverse population, including monocytes, macrophages, neutrophils, and dendritic cells. Their apoptosis, or programmed cell death, is tightly controlled by a complex interplay of signaling pathways that govern cell survival and death.

Negative regulation of myeloid cell apoptosis involves a series of molecular events that suppress or inhibit the apoptotic cascade. This process is crucial for maintaining the appropriate number and function of these cells, preventing excessive inflammation and immune dysregulation.

Key mechanisms involved in the negative regulation of myeloid cell apoptosis include:

1. **Survival Signaling Pathways:**
* **Growth Factor Receptors:** Activation of growth factor receptors, such as colony-stimulating factors (CSFs) and interleukins (ILs), promotes cell survival by activating downstream signaling pathways that inhibit apoptosis. These pathways involve proteins like STATs, PI3K, and Akt, which phosphorylate and activate anti-apoptotic proteins like Bcl-2 and Bcl-xL.
* **Toll-Like Receptors (TLRs):** Engagement of TLRs by microbial products, such as lipopolysaccharide (LPS), can trigger survival signaling cascades that prevent apoptosis in myeloid cells. These pathways often involve activation of NF-κB, a transcription factor that induces the expression of anti-apoptotic genes.
* **Integrin Signaling:** Adhesion of myeloid cells to the extracellular matrix via integrins can activate survival signaling pathways, contributing to their resistance to apoptosis.

2. **Inhibition of Apoptotic Caspase Activation:**
* **Inhibition of Caspase-9:** The caspase-9 protein is a key activator of the apoptotic cascade. Its activity can be inhibited by the anti-apoptotic protein XIAP (X-linked inhibitor of apoptosis protein), which binds to and blocks caspase-9.
* **Activation of Caspase Inhibitors:** Some anti-apoptotic proteins, such as cFLIP (cellular FLICE inhibitory protein), directly inhibit caspase activation by competing with caspase-8 for binding to the death-inducing signaling complex (DISC).

3. **Regulation of Mitochondrial Function:**
* **Bcl-2 Family Proteins:** The Bcl-2 family of proteins plays a crucial role in regulating mitochondrial outer membrane permeability. Anti-apoptotic proteins like Bcl-2 and Bcl-xL inhibit the release of cytochrome c from mitochondria, a key event in the apoptotic cascade. Pro-apoptotic proteins, such as Bax and Bak, promote mitochondrial permeabilization. The balance between these proteins determines the cell's fate.
* **IAPs:** IAPs can also directly interact with mitochondria, inhibiting the release of pro-apoptotic factors.

4. **Removal of Apoptotic Signals:**
* **Apoptotic Signal Clearance:** Myeloid cells can express receptors for apoptotic signals, such as Fas ligand (FasL), which can trigger apoptosis. However, these cells can also express decoy receptors that bind FasL without activating apoptosis, effectively removing the death signal.

In summary, negative regulation of myeloid cell apoptosis is a complex process involving multiple signaling pathways, protein interactions, and cellular responses. This intricate regulatory system ensures the proper maintenance and function of myeloid cells, contributing to immune homeostasis and tissue integrity. Dysregulation of this process can lead to various pathological conditions, including uncontrolled inflammation, autoimmune disorders, and cancer.'
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Proteins (3)

Compounds (67)