negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of intrinsic apoptotic signaling pathway in response to hydrogen peroxide. [GO_REF:0000058, GOC:TermGenie, PMID:18681888]

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that can trigger apoptosis, a programmed cell death process. The negative regulation of intrinsic apoptotic signaling pathway in response to H2O2 involves a complex interplay of various cellular mechanisms aimed at mitigating the damaging effects of this potent oxidant. Here's a detailed breakdown:

1. **Antioxidant Defense System:** Cells possess an arsenal of antioxidant enzymes and molecules that neutralize H2O2. Catalase, glutathione peroxidase, and superoxide dismutase play crucial roles in detoxifying H2O2 by converting it to less harmful molecules like water. These enzymes are upregulated in response to oxidative stress, enhancing the cell's capacity to manage H2O2 levels.

2. **Mitochondrial Membrane Potential Maintenance:** H2O2 can disrupt the mitochondrial membrane potential, a key factor in ATP production and apoptotic signaling. Cells employ mechanisms to preserve this potential, such as the activation of mitochondrial uncoupling proteins (UCPs) that dissipate the proton gradient across the inner mitochondrial membrane. This prevents excessive ROS production and minimizes the risk of mitochondrial dysfunction.

3. **Regulation of Pro-apoptotic Proteins:** The intrinsic apoptotic pathway is triggered by the release of cytochrome c from mitochondria. H2O2 can induce the release of this protein, activating caspase cascades that lead to cell death. However, cells have mechanisms to counteract this. For example, the anti-apoptotic protein Bcl-2 family members (Bcl-2, Bcl-xL) can inhibit cytochrome c release and prevent caspase activation.

4. **Activation of Survival Pathways:** H2O2 can also activate survival pathways that promote cell survival and counteract apoptotic signaling. These pathways involve the activation of transcription factors like NF-κB, which upregulates genes encoding anti-apoptotic proteins and antioxidant enzymes. Additionally, the activation of the PI3K/Akt pathway can inhibit the apoptotic cascade and promote cell survival.

5. **DNA Repair Mechanisms:** H2O2 can damage DNA, a critical trigger for apoptosis. Cells possess elaborate DNA repair mechanisms, including nucleotide excision repair and base excision repair, to repair oxidative DNA damage. This repair process minimizes the likelihood of DNA damage-induced apoptosis.

6. **Autophagy Induction:** Autophagy is a cellular process that removes damaged organelles and protein aggregates, contributing to cell survival. H2O2 can induce autophagy, which can help to remove damaged mitochondria and reduce ROS levels. This can help to prevent the accumulation of harmful molecules that would otherwise trigger apoptosis.

7. **Cell Cycle Arrest:** In response to H2O2, cells can arrest the cell cycle at various checkpoints, providing time for DNA repair and other cellular responses to take effect. This delay prevents the propagation of damaged cells and minimizes the risk of uncontrolled cell proliferation.

8. **Apoptosis-Inducing Factor (AIF):** AIF is a mitochondrial protein that can induce caspase-independent apoptosis. While H2O2 can trigger AIF release, cells may possess mechanisms to regulate AIF activity or its translocation to the nucleus, mitigating its apoptotic potential.

In summary, the negative regulation of the intrinsic apoptotic signaling pathway in response to H2O2 involves a multi-faceted response that includes antioxidant defenses, maintenance of mitochondrial membrane potential, regulation of pro-apoptotic proteins, activation of survival pathways, DNA repair mechanisms, autophagy induction, cell cycle arrest, and regulation of AIF activity. This complex interplay of cellular mechanisms highlights the intricate strategies cells employ to cope with oxidative stress and avoid premature demise.'
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Proteins (1)

Compounds (11)