Hypoxia-induced transcriptional differences in African and Asian versus European diabetic cybrids
Abstract Diabetic retinopathy (DR) is the most common diabetic microvascular complication and cause of blindness in adults under the age of 65. Our results suggest that, when comparing transcriptomes of cultures grown in hypoxic conditions versus room-air, cybrids containing mitochondria from Africa...
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| Format: | Article |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-30518-x |
| _version_ | 1797864987374387200 |
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| author | Andrew H. Dolinko Marilyn Chwa Kevin Schneider Mithalesh K. Singh Shari Atilano Jie Wu M. Cristina Kenney |
| author_facet | Andrew H. Dolinko Marilyn Chwa Kevin Schneider Mithalesh K. Singh Shari Atilano Jie Wu M. Cristina Kenney |
| author_sort | Andrew H. Dolinko |
| collection | DOAJ |
| description | Abstract Diabetic retinopathy (DR) is the most common diabetic microvascular complication and cause of blindness in adults under the age of 65. Our results suggest that, when comparing transcriptomes of cultures grown in hypoxic conditions versus room-air, cybrids containing mitochondria from African and Asian diabetic subjects ([Afr + Asi]/DM) have some uniquely different transcriptome profiles compared to European/diabetic (Euro/DM) cybrids (e.g., fatty acid metabolism: EnrichR rank 10 in [Afr + Asi]/DM, rank 85 in Euro/DM; Endocytosis: rank 25 in [Afr + Asi]/DM, rank 5 in Euro/DM; Ubiquitin Mediated Proteolysis: rank 34 in [Afr + Asi]/DM, rank 7 in Euro/DM). As determined by both RNA-seq and qRT-PCR results, transcription of the gene encoding oleoyl-ACP hydrolase (OLAH) was significantly increased in [Afr + Asi]/DM cybrids compared to Euro/DM cybrids in hypoxic conditions. Additionally, our results show that in hypoxic conditions, Euro/DM cybrids and [Afr + Asi]/DM cybrids show similar decreases in ROS production. All cybrids showed decreased ZO1-minus protein levels, but their phagocytic functions were not significantly altered in hypoxic conditions. In conclusion, our findings suggest that the "molecular memory" imparted by [Afr + Asi]/DM mtDNA may act through one of the molecular pathways seen in transcriptome analysis, such as fatty acid metabolism, without significantly changing essential RPE functions. |
| first_indexed | 2024-04-09T23:00:44Z |
| format | Article |
| id | doaj.art-685d2d01f82643eb895625f5bfce2512 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T23:00:44Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-685d2d01f82643eb895625f5bfce25122023-03-22T10:59:14ZengNature PortfolioScientific Reports2045-23222023-03-0113111110.1038/s41598-023-30518-xHypoxia-induced transcriptional differences in African and Asian versus European diabetic cybridsAndrew H. Dolinko0Marilyn Chwa1Kevin Schneider2Mithalesh K. Singh3Shari Atilano4Jie Wu5M. Cristina Kenney6Department of Pathology and Laboratory Medicine, University of California IrvineDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California IrvineDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California IrvineDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California IrvineDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California IrvineDepartment of Biological Chemistry, University of California IrvineDepartment of Pathology and Laboratory Medicine, University of California IrvineAbstract Diabetic retinopathy (DR) is the most common diabetic microvascular complication and cause of blindness in adults under the age of 65. Our results suggest that, when comparing transcriptomes of cultures grown in hypoxic conditions versus room-air, cybrids containing mitochondria from African and Asian diabetic subjects ([Afr + Asi]/DM) have some uniquely different transcriptome profiles compared to European/diabetic (Euro/DM) cybrids (e.g., fatty acid metabolism: EnrichR rank 10 in [Afr + Asi]/DM, rank 85 in Euro/DM; Endocytosis: rank 25 in [Afr + Asi]/DM, rank 5 in Euro/DM; Ubiquitin Mediated Proteolysis: rank 34 in [Afr + Asi]/DM, rank 7 in Euro/DM). As determined by both RNA-seq and qRT-PCR results, transcription of the gene encoding oleoyl-ACP hydrolase (OLAH) was significantly increased in [Afr + Asi]/DM cybrids compared to Euro/DM cybrids in hypoxic conditions. Additionally, our results show that in hypoxic conditions, Euro/DM cybrids and [Afr + Asi]/DM cybrids show similar decreases in ROS production. All cybrids showed decreased ZO1-minus protein levels, but their phagocytic functions were not significantly altered in hypoxic conditions. In conclusion, our findings suggest that the "molecular memory" imparted by [Afr + Asi]/DM mtDNA may act through one of the molecular pathways seen in transcriptome analysis, such as fatty acid metabolism, without significantly changing essential RPE functions.https://doi.org/10.1038/s41598-023-30518-x |
| spellingShingle | Andrew H. Dolinko Marilyn Chwa Kevin Schneider Mithalesh K. Singh Shari Atilano Jie Wu M. Cristina Kenney Hypoxia-induced transcriptional differences in African and Asian versus European diabetic cybrids Scientific Reports |
| title | Hypoxia-induced transcriptional differences in African and Asian versus European diabetic cybrids |
| title_full | Hypoxia-induced transcriptional differences in African and Asian versus European diabetic cybrids |
| title_fullStr | Hypoxia-induced transcriptional differences in African and Asian versus European diabetic cybrids |
| title_full_unstemmed | Hypoxia-induced transcriptional differences in African and Asian versus European diabetic cybrids |
| title_short | Hypoxia-induced transcriptional differences in African and Asian versus European diabetic cybrids |
| title_sort | hypoxia induced transcriptional differences in african and asian versus european diabetic cybrids |
| url | https://doi.org/10.1038/s41598-023-30518-x |
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