Both 3,3′,5-triiodothyronine and 3,5-diodo-L-thyronine Are Able to Repair Mitochondrial DNA Damage but by Different Mechanisms
This study evaluated the effect of 3,5-diiodo-L-thyronine (T2) and 3,5,3′-triiodo-L-thyronine (T3) on rat liver mitochondrial DNA (mtDNA) oxidative damage and repair and to investigate their ability to induce protective effects against oxidative stress. Control rats, rats receiving a daily injection...
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| Language: | English |
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2019.00216/full |
| _version_ | 1811286750353424384 |
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| author | Federica Cioffi Rosalba Senese Giuseppe Petito Pasquale Lasala Pieter de Lange Elena Silvestri Assunta Lombardi Maria Moreno Fernando Goglia Antonia Lanni |
| author_facet | Federica Cioffi Rosalba Senese Giuseppe Petito Pasquale Lasala Pieter de Lange Elena Silvestri Assunta Lombardi Maria Moreno Fernando Goglia Antonia Lanni |
| author_sort | Federica Cioffi |
| collection | DOAJ |
| description | This study evaluated the effect of 3,5-diiodo-L-thyronine (T2) and 3,5,3′-triiodo-L-thyronine (T3) on rat liver mitochondrial DNA (mtDNA) oxidative damage and repair and to investigate their ability to induce protective effects against oxidative stress. Control rats, rats receiving a daily injection of T2 (N+T2) for 1 week and rats receiving a daily injection of T3 (N+T3) for 1 week, were used throughout the study. In the liver, mtDNA oxidative damage [by measuring mtDNA lesion frequency and expression of DNA polymerase γ (POLG)], mtDNA copy number, mitochondrial biogenesis [by measuring amplification of mtDNA/nDNA and expression of peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α)], and oxidative stress [by measuring serum levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG)] were detected. T2 reduces mtDNA lesion frequency and increases the expression of POLG, and it does not change the mtDNA copy number, the expression of PGC-1α, or the serum levels of 8-OHdG. Therefore, T2, by stimulating the major mtDNA repair enzyme, maintains genomic integrity. Similar to T2, T3 decreases mtDNA lesion frequency but increases the serum levels of 8-OHdG, and it decreases the expression of POLG. Moreover, as expected, T3 increases the mtDNA copy number and the expression of PGC-1α. Thus, in T3-treated rats, the increase of 8-OHdG and the decrease of POLG indicate that there is increased oxidative damage and that the decreased mtDNA lesion frequency might be a consequence of increased mitochondrial biogenesis. These data demonstrate that both T2 and T3 are able to decrease in the liver mtDNA oxidative damage, but they act via different mechanisms. |
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| id | doaj.art-771877fba2de4ae98bf4ea23adf5e6b0 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T03:05:12Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-771877fba2de4ae98bf4ea23adf5e6b02022-12-22T03:05:16ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-04-011010.3389/fendo.2019.00216431696Both 3,3′,5-triiodothyronine and 3,5-diodo-L-thyronine Are Able to Repair Mitochondrial DNA Damage but by Different MechanismsFederica Cioffi0Rosalba Senese1Giuseppe Petito2Pasquale Lasala3Pieter de Lange4Elena Silvestri5Assunta Lombardi6Maria Moreno7Fernando Goglia8Antonia Lanni9Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Benevento, ItalyDipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli Studi della Campania Luigi Vanvitelli, Caserta, ItalyDipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli Studi della Campania Luigi Vanvitelli, Caserta, ItalyDipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Benevento, ItalyDipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli Studi della Campania Luigi Vanvitelli, Caserta, ItalyDipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Benevento, ItalyDipartimento di Biologia, Università degli Studi di Napoli Federico II, Naples, ItalyDipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Benevento, ItalyDipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Benevento, ItalyDipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli Studi della Campania Luigi Vanvitelli, Caserta, ItalyThis study evaluated the effect of 3,5-diiodo-L-thyronine (T2) and 3,5,3′-triiodo-L-thyronine (T3) on rat liver mitochondrial DNA (mtDNA) oxidative damage and repair and to investigate their ability to induce protective effects against oxidative stress. Control rats, rats receiving a daily injection of T2 (N+T2) for 1 week and rats receiving a daily injection of T3 (N+T3) for 1 week, were used throughout the study. In the liver, mtDNA oxidative damage [by measuring mtDNA lesion frequency and expression of DNA polymerase γ (POLG)], mtDNA copy number, mitochondrial biogenesis [by measuring amplification of mtDNA/nDNA and expression of peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α)], and oxidative stress [by measuring serum levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG)] were detected. T2 reduces mtDNA lesion frequency and increases the expression of POLG, and it does not change the mtDNA copy number, the expression of PGC-1α, or the serum levels of 8-OHdG. Therefore, T2, by stimulating the major mtDNA repair enzyme, maintains genomic integrity. Similar to T2, T3 decreases mtDNA lesion frequency but increases the serum levels of 8-OHdG, and it decreases the expression of POLG. Moreover, as expected, T3 increases the mtDNA copy number and the expression of PGC-1α. Thus, in T3-treated rats, the increase of 8-OHdG and the decrease of POLG indicate that there is increased oxidative damage and that the decreased mtDNA lesion frequency might be a consequence of increased mitochondrial biogenesis. These data demonstrate that both T2 and T3 are able to decrease in the liver mtDNA oxidative damage, but they act via different mechanisms.https://www.frontiersin.org/article/10.3389/fendo.2019.00216/fullmitochondrialivermtDNAoxidative damageiodothyronines |
| spellingShingle | Federica Cioffi Rosalba Senese Giuseppe Petito Pasquale Lasala Pieter de Lange Elena Silvestri Assunta Lombardi Maria Moreno Fernando Goglia Antonia Lanni Both 3,3′,5-triiodothyronine and 3,5-diodo-L-thyronine Are Able to Repair Mitochondrial DNA Damage but by Different Mechanisms Frontiers in Endocrinology mitochondria liver mtDNA oxidative damage iodothyronines |
| title | Both 3,3′,5-triiodothyronine and 3,5-diodo-L-thyronine Are Able to Repair Mitochondrial DNA Damage but by Different Mechanisms |
| title_full | Both 3,3′,5-triiodothyronine and 3,5-diodo-L-thyronine Are Able to Repair Mitochondrial DNA Damage but by Different Mechanisms |
| title_fullStr | Both 3,3′,5-triiodothyronine and 3,5-diodo-L-thyronine Are Able to Repair Mitochondrial DNA Damage but by Different Mechanisms |
| title_full_unstemmed | Both 3,3′,5-triiodothyronine and 3,5-diodo-L-thyronine Are Able to Repair Mitochondrial DNA Damage but by Different Mechanisms |
| title_short | Both 3,3′,5-triiodothyronine and 3,5-diodo-L-thyronine Are Able to Repair Mitochondrial DNA Damage but by Different Mechanisms |
| title_sort | both 3 3 5 triiodothyronine and 3 5 diodo l thyronine are able to repair mitochondrial dna damage but by different mechanisms |
| topic | mitochondria liver mtDNA oxidative damage iodothyronines |
| url | https://www.frontiersin.org/article/10.3389/fendo.2019.00216/full |
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