negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of intrinsic apoptotic signaling pathway in response to nitrosative stress. [GO_REF:0000058, GOC:bf, GOC:PARL, GOC:TermGenie, PMID:14752510]

Nitrosative stress, a condition characterized by elevated levels of reactive nitrogen species (RNS) such as nitric oxide (NO), can trigger intrinsic apoptotic signaling pathways leading to cell death. This pathway involves the activation of caspases, a family of cysteine proteases, ultimately leading to the breakdown of cellular components and programmed cell death. Negative regulation of this pathway involves a complex interplay of various cellular mechanisms aimed at dampening the deleterious effects of nitrosative stress and preventing unwanted apoptosis.

These regulatory mechanisms include:

1. **Antioxidant Defense:** Cells employ various antioxidant systems to neutralize RNS and prevent their accumulation. Enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase scavenge reactive oxygen species (ROS), which can contribute to nitrosative stress.

2. **Redox Homeostasis:** Maintaining redox balance is crucial for cell survival. Cells utilize redox-sensitive transcription factors like Nrf2, which upon activation, induce the expression of antioxidant and detoxifying enzymes to counteract oxidative and nitrosative stress.

3. **Mitochondrial Regulation:** Mitochondria play a central role in intrinsic apoptosis, acting as both a source and target of nitrosative stress. Cells employ mechanisms to control mitochondrial function, such as the regulation of mitochondrial membrane potential, the expression of anti-apoptotic Bcl-2 family proteins, and the activation of pro-survival signaling pathways.

4. **Caspase Inhibition:** Caspases, the key executioners of apoptosis, can be inhibited by various mechanisms. Specific caspase inhibitors, anti-apoptotic proteins, and the activation of pro-survival signaling pathways can all contribute to blocking caspase activation and preventing the progression of apoptosis.

5. **DNA Repair:** Nitrosative stress can damage DNA, leading to apoptosis. Cells possess DNA repair mechanisms that can repair damaged DNA, reducing the risk of apoptosis triggered by DNA damage.

6. **Autophagy:** Autophagy, a cellular process of self-eating, can remove damaged organelles and protein aggregates, contributing to cell survival under stress.

7. **Signal Transduction Pathways:** Several signal transduction pathways, such as the PI3K/Akt and MAPK pathways, are involved in cell survival and can be activated in response to nitrosative stress to counteract apoptotic signaling.

These regulatory mechanisms work together to dampen the apoptotic response triggered by nitrosative stress, allowing cells to survive and maintain homeostasis.'
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Proteins (1)

Compounds (213)