International Journal of Molecular Medical Science, 2024, Vol.14, No.6, 324-341 http://medscipublisher.com/index.php/ijmms 331 caspase-9 and caspase-3, leading to the execution of apoptosis (Cao et al., 2010; Wu et al., 2014). The intrinsic pathway is often regulated by the balance between pro-apoptotic (e.g., Bax) and anti-apoptotic (e.g., Bcl-2) proteins (Figure 6) (Cui et al., 2016; Wan et al., 2020). Figure 6 Mechanism diagram of cell apoptosis signaling pathway Another significant pathway is the extrinsic death receptor pathway, which involves the binding of ligands to death receptors such as FAS, leading to the activation of caspase-8 and subsequent activation of downstream caspases (Yu et al., 2020). This pathway can also interact with the intrinsic pathway through the cleavage of Bid, a pro-apoptotic Bcl-2 family member, linking the two apoptotic mechanisms (Carneiro and El-Deiry, 2020). Additionally, Sanghuangporus polysaccharides have been shown to modulate other signaling pathways, such as the PI3K/AKT and MAPK pathways. These pathways play crucial roles in cell survival and proliferation, and their inhibition can promote apoptosis. For instance, the polysaccharide from Grifola frondosa (GFP-A) was found to inhibit the PI3K/AKT pathway and activate the MAPK pathway, leading to increased apoptosis in HT-29 cells (Bie et al., 2020). Similarly, the AMPK/PI3K/mTOR pathway is involved in the regulation of apoptosis and autophagy, with polysaccharides from Pleurotus nebrodensis (PN50G) shown to activate AMPK and inhibit PI3K/AKT, promoting apoptosis in A549 cells (Cui et al., 2016). 4.3 Expression of apoptosis-related genes and proteins The expression of apoptosis-related genes and proteins is a critical aspect of understanding the molecular mechanisms of Sanghuangporus polysaccharides-induced apoptosis. Key genes involved in the intrinsic pathway include Bax, Bcl-2, and caspases. Studies have shown that treatment with Sanghuangporus polysaccharides leads to the upregulation of Bax and downregulation of Bcl-2, promoting the release of cytochrome c and activation of caspase-9 and caspase-3 (Wu et al., 2014; Wan et al., 2020). This regulation of gene expression is crucial for the initiation and execution of apoptosis. In the extrinsic pathway, the expression of death receptors such as FAS and their ligands (FAS-L) is upregulated, leading to the activation of caspase-8 and subsequent apoptosis (Yu et al., 2020). The interaction between the intrinsic and extrinsic pathways is further evidenced by the cleavage of Bid, linking the two apoptotic mechanisms (Song et al., 2014).
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