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Inhibition of apoptosis by ascorbic and dehydroascorbic acids in Xenopus egg extracts
Tomohiro Saitoh1, Yuichi Tsuchiya2, Toshihiko Kinoshita1
1Department of Obstetrics and Gynecology Toho University Medical Center Sakura Hospital 564-1 Shimoshizu Sakura-shi 285-8741 Chiba Japan.
Reproductive Medicine and Biology
|April 28, 2018
Summary
Ascorbic acid’s anti-apoptotic effects in Xenopus egg extracts stem from cytoplasmic acidification, not antioxidant activity. Its oxidized form, dehydroascorbic acid, directly inhibits caspases, suggesting a novel mechanism for preventing cell death.
Area of Science:
- Cell Biology
- Biochemistry
- Developmental Biology
Background:
- Ascorbic acid enhances mammalian egg viability post-ovulation, but its survival mechanisms remain unclear.
- Apoptosis pathways are conserved across species, making Xenopus egg extracts a suitable model for biochemical analysis.
Purpose of the Study:
- To investigate the direct intracellular effects of ascorbic acid on apoptosis in Xenopus egg cytoplasmic extracts.
- To elucidate the molecular mechanisms underlying ascorbic acid's pro-survival effects.
Main Methods:
- Xenopus egg extracts were incubated to induce spontaneous apoptosis.
- The study examined the impact of ascorbic acid on cytochrome c release, caspase activation, and substrate cleavage.
- Signal transduction pathways, including proteolysis and protein phosphorylation, were analyzed.
Main Results:
- Ascorbic acid did not prevent cytochrome c release but inhibited caspase activation and substrate cleavage.
- It blocked the proteolysis of apoptosis inhibitors and dephosphorylation of p42 MAP kinase.
- Dehydroascorbic acid and acetate showed similar effects, indicating acidity as a primary factor; dehydroascorbic acid directly inhibited caspases in vitro.
Conclusions:
- The anti-apoptotic effect of ascorbic acid in Xenopus egg extracts is primarily attributed to cytoplasmic acidification.
- Oxidative conversion to dehydroascorbic acid may inhibit apoptosis by directly suppressing caspase activity.
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