Redox-dependent purine degradation triggers postnatal loss of cardiac regeneration potential
Postnatal cardiomyocyte cell cycle withdrawal is a critical step wherein the mammalian heart loses regenerative potential after birth. Here, we conducted interspecies multi-omic comparisons between the mouse heart and that of the opossum, which have different postnatal time-windows for cardiomyocyte...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231724004208 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841542505931210752 |
|---|---|
| author | Yuichi Saito Yuki Sugiura Akane Sakaguchi Tai Sada Chihiro Nishiyama Rae Maeda Mari Kaneko Hiroshi Kiyonari Wataru Kimura |
| author_facet | Yuichi Saito Yuki Sugiura Akane Sakaguchi Tai Sada Chihiro Nishiyama Rae Maeda Mari Kaneko Hiroshi Kiyonari Wataru Kimura |
| author_sort | Yuichi Saito |
| collection | DOAJ |
| description | Postnatal cardiomyocyte cell cycle withdrawal is a critical step wherein the mammalian heart loses regenerative potential after birth. Here, we conducted interspecies multi-omic comparisons between the mouse heart and that of the opossum, which have different postnatal time-windows for cardiomyocyte cell cycle withdrawal. Xanthine metabolism was activated in both postnatal hearts in parallel with cardiomyocyte cell cycle arrest. The pentose phosphate pathway (PPP) which produces NADPH was found to decrease simultaneously. Postnatal myocardial tissues became oxidized accordingly, and administration of antioxidants to neonatal mice altered the PPP and suppressed the postnatal activation of cardiac xanthine metabolism. These results suggest a redox-driven postnatal switch from purine synthesis to degradation in the heart. Importantly, inhibition of xanthine metabolism in the postnatal heart extended postnatal duration of cardiomyocyte proliferation and maintained postnatal heart regeneration potential in mice. These findings highlight a novel role of xanthine metabolism as a redox-dependent metabolic regulator of cardiac regeneration potential. |
| format | Article |
| id | doaj-art-e55e8c6eb289406ab4ed8a7471804daa |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-e55e8c6eb289406ab4ed8a7471804daa2025-01-14T04:12:04ZengElsevierRedox Biology2213-23172025-02-0179103442Redox-dependent purine degradation triggers postnatal loss of cardiac regeneration potentialYuichi Saito0Yuki Sugiura1Akane Sakaguchi2Tai Sada3Chihiro Nishiyama4Rae Maeda5Mari Kaneko6Hiroshi Kiyonari7Wataru Kimura8Laboratory for Heart Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan; Corresponding author.Multiomics Platform, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan; Human Biology Microbiome Quantum Research Center (WPI-Bio2Q), Keio University School of Medicine, Tokyo, JapanLaboratory for Heart Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, JapanLaboratory for Heart Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, JapanLaboratory for Heart Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, JapanMultiomics Platform, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, JapanLaboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, 650-0047, JapanLaboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, 650-0047, JapanLaboratory for Heart Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan; Corresponding author.Postnatal cardiomyocyte cell cycle withdrawal is a critical step wherein the mammalian heart loses regenerative potential after birth. Here, we conducted interspecies multi-omic comparisons between the mouse heart and that of the opossum, which have different postnatal time-windows for cardiomyocyte cell cycle withdrawal. Xanthine metabolism was activated in both postnatal hearts in parallel with cardiomyocyte cell cycle arrest. The pentose phosphate pathway (PPP) which produces NADPH was found to decrease simultaneously. Postnatal myocardial tissues became oxidized accordingly, and administration of antioxidants to neonatal mice altered the PPP and suppressed the postnatal activation of cardiac xanthine metabolism. These results suggest a redox-driven postnatal switch from purine synthesis to degradation in the heart. Importantly, inhibition of xanthine metabolism in the postnatal heart extended postnatal duration of cardiomyocyte proliferation and maintained postnatal heart regeneration potential in mice. These findings highlight a novel role of xanthine metabolism as a redox-dependent metabolic regulator of cardiac regeneration potential.http://www.sciencedirect.com/science/article/pii/S2213231724004208Cell cycle arrestHeart regenerationInterspecies comparisonPentose phosphate pathwayXanthine metabolism |
| spellingShingle | Yuichi Saito Yuki Sugiura Akane Sakaguchi Tai Sada Chihiro Nishiyama Rae Maeda Mari Kaneko Hiroshi Kiyonari Wataru Kimura Redox-dependent purine degradation triggers postnatal loss of cardiac regeneration potential Redox Biology Cell cycle arrest Heart regeneration Interspecies comparison Pentose phosphate pathway Xanthine metabolism |
| title | Redox-dependent purine degradation triggers postnatal loss of cardiac regeneration potential |
| title_full | Redox-dependent purine degradation triggers postnatal loss of cardiac regeneration potential |
| title_fullStr | Redox-dependent purine degradation triggers postnatal loss of cardiac regeneration potential |
| title_full_unstemmed | Redox-dependent purine degradation triggers postnatal loss of cardiac regeneration potential |
| title_short | Redox-dependent purine degradation triggers postnatal loss of cardiac regeneration potential |
| title_sort | redox dependent purine degradation triggers postnatal loss of cardiac regeneration potential |
| topic | Cell cycle arrest Heart regeneration Interspecies comparison Pentose phosphate pathway Xanthine metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2213231724004208 |
| work_keys_str_mv | AT yuichisaito redoxdependentpurinedegradationtriggerspostnatallossofcardiacregenerationpotential AT yukisugiura redoxdependentpurinedegradationtriggerspostnatallossofcardiacregenerationpotential AT akanesakaguchi redoxdependentpurinedegradationtriggerspostnatallossofcardiacregenerationpotential AT taisada redoxdependentpurinedegradationtriggerspostnatallossofcardiacregenerationpotential AT chihironishiyama redoxdependentpurinedegradationtriggerspostnatallossofcardiacregenerationpotential AT raemaeda redoxdependentpurinedegradationtriggerspostnatallossofcardiacregenerationpotential AT marikaneko redoxdependentpurinedegradationtriggerspostnatallossofcardiacregenerationpotential AT hiroshikiyonari redoxdependentpurinedegradationtriggerspostnatallossofcardiacregenerationpotential AT watarukimura redoxdependentpurinedegradationtriggerspostnatallossofcardiacregenerationpotential |