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  • Of note the intracellular egg compartment exhibiting SA gal

    2022-05-12

    Of note, the intracellular egg compartment exhibiting SA-β-gal activity also exhibits lipofuscin auto-fluorescence (Fig. 6B), and it is co-stained with the lipid-specific dye SBB (Supplemental Fig. 5). On the one hand, these findings reflect the fact that the pool of yolk protein contains lipoproteins, such as lipovitellin, with the bound lipid (Finn, 2007). On the other hand, lipovitellins, which represent the product of incomplete digestion of vitellogenin at low pH, can be a source of lipofuscin in aging Xenopus eggs. It was found that lipofuscin, a non-degradable complex of oxidized proteins, lipids and metals, accumulates in lysosomes of damaged and senescent cells. Alongside with SA-β-gal activity increase, lipofuscin aggregation is considered to be a hallmark of cell senescence and aging (Jung et al., 2007). Recently, lipofuscin staining with SBB or its analogs was proposed as a novel biomarker to detect cellular senescence in different clinical samples and archival tissues (Georgakopoulou et al., 2013; Evangelou et al., 2017). In connection with our work, it would be interesting to investigate in future studies the dynamics of lipofuscin accumulation in aging Xenopus oocytes and eggs. The increase of SA-β-gal activity in senescent somatic Idoxuridine was previously linked to the increased number of lysosomes, elevated lysosomal activity, and/or increased enzyme content (Gary and Kindell, 2005; Kurz et al., 2000). However, it is most unlikely that SA-β-gal content increases in the process of Xenopus egg aging. It was demonstrated recently that numerous cytoplasmic mRNAs coding for proteins classified into different functional types are robustly degraded in aging Xenopus eggs (Tokmakov et al., 2017). The degradation is evident 24 h after progesterone administration and no intact mRNA molecules can be detected in the egg cytoplasm by 48 h. On the other hand, considering predominant localization of SA-β-gal, it is quite natural to suggest that the increase of enzyme activity observed in the aging eggs (Fig. 3D, E) might be related to age-associated changes of the endosomal yolk platelet compartment. In general, activation of lysosome biogenesis and autophagy, which is thought to help maintain intracellular homeostasis, is seen in response to cellular distresses that lead to apoptosis and cell death (Moore et al., 2006). Recently, it was reported that post-ovulatory aging of mouse oocytes is accompanied by the increase in the abundance of large autophagic lysosomes (McGinnis et al., 2014). The study suggested that the progressive increase in lysosomal autophagy would significantly reduce fertilization and developmental potential of aged oocytes. SA-β-gal activity was found to be elevated both in particulate and cytosolic fractions of aging eggs, and the increase was far more prominent in the particulate fraction (Fig. 7). However, our present work failed to reveal any statistically significant increase in the size of SPiDER-β-gal- and LysoTracker-stained particles (Fig. 8D). Markedly, the LysoTracker signal from this fraction was also increased in aging Xenopus eggs (Fig. 8C), suggesting a link between endosomal pH and SA-β-gal activity. Using the specific inhibitor of V-ATPase bafilomycin A1, we confirmed that pH changes in the endosomal compartment can modulate SA-β-gal activity (Fig. 9). It was reported previously that an acidic internal pH of yolk platelets in Xenopus oocytes is maintained by the activity of bafilomycin A1-sensitive vacuolar proton-ATPase (Fagotto and Maxfield, 1994a). Taken together, our results imply that acidification of the endosomal compartment during egg aging may be responsible for the observed increase of SA-β-gal activity in these cells. In this connection, an evidence has been presented that pH is the key regulator of yolk turnover. It was found that the mature yolk platelets are mildly acidic (around pH 5.6), (Fagotto and Maxfield, 1994a). This pH is thought to be required for the partial cleavage of vitellogenin to yolk proteins and maintaining the integrity of the yolk platelets. However, it does not promote yolk degradation because acid hydrolases, and especially proteinases, present in the yolk platelets are inactive at the mildly acidic pH. It was further demonstrated that the yolk platelets become progressively more acidic (pH < 5.0) during embryogenesis, and the acidification correlates with yolk degradation (Fagotto and Maxfield, 1994b). In addition, yolk degradation is blocked when acidification is inhibited with an inhibitor of the vacuolar proton ATPase. Cyclic-AMP was found to increase acidification the yolk platelets, indicating that their pH can be regulated by intracellular second messengers (Fagotto and Maxfield, 1994a). Altogether, these data demonstrate that regulated acidification of yolk platelets controls the processes of yolk accumulation and degradation in Xenopus oocytes and embryos. Now, the results of our study suggest that acidification of endosomal yolk platelets may also occur during Xenopus egg aging. At present, no reports have been presented concerning pH changes in the lysosomal compartment of eggs during their aging and apoptosis. However, a recent study demonstrated that post-ovulatory aging of mouse oocytes affects lysosome biogenesis (McGinnis et al., 2014). Further investigations are necessary to elucidate functional and molecular changes in lysosomal compartment during oocyte and egg aging.