African and Asian Mitochondrial DNA Haplogroups Confer Resistance Against Diabetic Stresses on Retinal Pigment Epithelial Cybrid Cells In Vitro

Diabetic retinopathy (DR) is the most common cause of blindness for individuals under the age of 65. This loss of vision can be due to ischemia, neovascularization, and/or diabetic macular edema, which are caused by breakdown of the blood–retina barrier at the level of the retinal pigment epithelium...

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Published inMolecular neurobiology Vol. 57; no. 3; pp. 1636 - 1655
Main Authors Dolinko, Andrew H., Chwa, Marilyn, Atilano, Shari R., Kenney, M. Cristina
Format Journal Article
LanguageEnglish
Published New York Springer US 01.03.2020
Springer Nature B.V
Subjects
Adult
Aged
Apoptosis
Asian Americans
Asian People
Azacytidine
Biomedical and Life Sciences
Biomedicine
Blindness
Cell Biology
Cell lines
Cells, Cultured
Cybrids
Demethylation
Deoxyribonucleic acid
Diabetes
Diabetes mellitus
Diabetes Mellitus - metabolism
Diabetic retinopathy
Diabetic Retinopathy - genetics
DNA
DNA methylation
DNA, Mitochondrial - genetics
Edema
Epithelium
Female
Humans
Hyperglycemia
Hypoxia
Ischemia
Macular Edema - genetics
Male
Metabolism
Middle Aged
Mitochondria - metabolism
Mitochondrial DNA
Neurobiology
Neurology
Neurosciences
Polymorphism, Single Nucleotide - genetics
Population studies
Retina
Retinal pigment epithelium
Retinal Pigment Epithelium - cytology
Retinopathy
Signal Transduction - genetics
Single-nucleotide polymorphism
Vascularization
White People
Retinal pigment epithelial cells
African and Asian mitochondrial DNA haplogroups
Diabetic retinopathy (DR)
Cybrid cell model
Hyperglycemic and hypoxic stresses
Online AccessGet full text

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Abstract Diabetic retinopathy (DR) is the most common cause of blindness for individuals under the age of 65. This loss of vision can be due to ischemia, neovascularization, and/or diabetic macular edema, which are caused by breakdown of the blood–retina barrier at the level of the retinal pigment epithelium (RPE) and inner retinal vasculature. The prevalence of diabetes and its complications differ between Caucasian-Americans and certain minority populations, such as African-Americans and Asian-Americans. Individuals can be classified by their mitochondrial haplogroups, which are collections of single nucleotide polymorphisms (SNPs) in mitochondrial DNA (mtDNA) representing ancient geographic origins of populations. In this study, we compared the responses of diabetic human RPE cybrids, cell lines containing identical nuclei but mitochondria from either European (maternal European) or maternal African or Asian individuals, to hypoxia and high glucose levels. The African and Asian diabetic ([Afr+Asi]/DM) cybrids showed (1) resistance to both hyperglycemic and hypoxic stresses; (2) downregulation of pro-apoptotic indicator BAX ; (3) upregulation of DNA methylation genes, such as DNMT3A and DNMT3B ; and (4) resistance to DNA demethylation by the methylation inhibitor 5-Aza-2′-deoxycytidine (5-Aza-dC) compared to European diabetic (Euro/DM) cybrids. Our findings suggest that mitochondria from African and Asian diabetic subjects possess a “metabolic memory” that confers resistance against hyperglycemia, hypoxia, and demethylation, and that this “metabolic memory” can be transferred into the RPE cybrid cell lines in vitro.
AbstractList Diabetic retinopathy (DR) is the most common cause of blindness for individuals under the age of 65. This loss of vision can be due to ischemia, neovascularization, and/or diabetic macular edema, which are caused by breakdown of the blood-retina barrier at the level of the retinal pigment epithelium (RPE) and inner retinal vasculature. The prevalence of diabetes and its complications differ between Caucasian-Americans and certain minority populations, such as African-Americans and Asian-Americans. Individuals can be classified by their mitochondrial haplogroups, which are collections of single nucleotide polymorphisms (SNPs) in mitochondrial DNA (mtDNA) representing ancient geographic origins of populations. In this study, we compared the responses of diabetic human RPE cybrids, cell lines containing identical nuclei but mitochondria from either European (maternal European) or maternal African or Asian individuals, to hypoxia and high glucose levels. The African and Asian diabetic ([Afr+Asi]/DM) cybrids showed (1) resistance to both hyperglycemic and hypoxic stresses; (2) downregulation of pro-apoptotic indicator BAX; (3) upregulation of DNA methylation genes, such as DNMT3A and DNMT3B; and (4) resistance to DNA demethylation by the methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-dC) compared to European diabetic (Euro/DM) cybrids. Our findings suggest that mitochondria from African and Asian diabetic subjects possess a "metabolic memory" that confers resistance against hyperglycemia, hypoxia, and demethylation, and that this "metabolic memory" can be transferred into the RPE cybrid cell lines in vitro.Diabetic retinopathy (DR) is the most common cause of blindness for individuals under the age of 65. This loss of vision can be due to ischemia, neovascularization, and/or diabetic macular edema, which are caused by breakdown of the blood-retina barrier at the level of the retinal pigment epithelium (RPE) and inner retinal vasculature. The prevalence of diabetes and its complications differ between Caucasian-Americans and certain minority populations, such as African-Americans and Asian-Americans. Individuals can be classified by their mitochondrial haplogroups, which are collections of single nucleotide polymorphisms (SNPs) in mitochondrial DNA (mtDNA) representing ancient geographic origins of populations. In this study, we compared the responses of diabetic human RPE cybrids, cell lines containing identical nuclei but mitochondria from either European (maternal European) or maternal African or Asian individuals, to hypoxia and high glucose levels. The African and Asian diabetic ([Afr+Asi]/DM) cybrids showed (1) resistance to both hyperglycemic and hypoxic stresses; (2) downregulation of pro-apoptotic indicator BAX; (3) upregulation of DNA methylation genes, such as DNMT3A and DNMT3B; and (4) resistance to DNA demethylation by the methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-dC) compared to European diabetic (Euro/DM) cybrids. Our findings suggest that mitochondria from African and Asian diabetic subjects possess a "metabolic memory" that confers resistance against hyperglycemia, hypoxia, and demethylation, and that this "metabolic memory" can be transferred into the RPE cybrid cell lines in vitro.
Diabetic retinopathy (DR) is the most common cause of blindness for individuals under the age of 65. This loss of vision can be due to ischemia, neovascularization, and/or diabetic macular edema, which are caused by breakdown of the blood-retina barrier at the level of the retinal pigment epithelium (RPE) and inner retinal vasculature. The prevalence of diabetes and its complications differ between Caucasian-Americans and certain minority populations, such as African-Americans and Asian-Americans. Individuals can be classified by their mitochondrial haplogroups, which are collections of single nucleotide polymorphisms (SNPs) in mitochondrial DNA (mtDNA) representing ancient geographic origins of populations. In this study, we compared the responses of diabetic human RPE cybrids, cell lines containing identical nuclei but mitochondria from either European (maternal European) or maternal African or Asian individuals, to hypoxia and high glucose levels. The African and Asian diabetic ([Afr+Asi]/DM) cybrids showed (1) resistance to both hyperglycemic and hypoxic stresses; (2) downregulation of pro-apoptotic indicator BAX; (3) upregulation of DNA methylation genes, such as DNMT3A and DNMT3B; and (4) resistance to DNA demethylation by the methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-dC) compared to European diabetic (Euro/DM) cybrids. Our findings suggest that mitochondria from African and Asian diabetic subjects possess a "metabolic memory" that confers resistance against hyperglycemia, hypoxia, and demethylation, and that this "metabolic memory" can be transferred into the RPE cybrid cell lines in vitro.
Diabetic retinopathy (DR) is the most common cause of blindness for individuals under the age of 65. This loss of vision can be due to ischemia, neovascularization, and/or diabetic macular edema, which are caused by breakdown of the blood–retina barrier at the level of the retinal pigment epithelium (RPE) and inner retinal vasculature. The prevalence of diabetes and its complications differ between Caucasian-Americans and certain minority populations, such as African-Americans and Asian-Americans. Individuals can be classified by their mitochondrial haplogroups, which are collections of single nucleotide polymorphisms (SNPs) in mitochondrial DNA (mtDNA) representing ancient geographic origins of populations. In this study, we compared the responses of diabetic human RPE cybrids, cell lines containing identical nuclei but mitochondria from either European (maternal European) or maternal African or Asian individuals, to hypoxia and high glucose levels. The African and Asian diabetic ([Afr+Asi]/DM) cybrids showed (1) resistance to both hyperglycemic and hypoxic stresses; (2) downregulation of pro-apoptotic indicator BAX ; (3) upregulation of DNA methylation genes, such as DNMT3A and DNMT3B ; and (4) resistance to DNA demethylation by the methylation inhibitor 5-Aza-2′-deoxycytidine (5-Aza-dC) compared to European diabetic (Euro/DM) cybrids. Our findings suggest that mitochondria from African and Asian diabetic subjects possess a “metabolic memory” that confers resistance against hyperglycemia, hypoxia, and demethylation, and that this “metabolic memory” can be transferred into the RPE cybrid cell lines in vitro.
Diabetic retinopathy (DR) is the most common cause of blindness for individuals under the age of 65. This loss of vision can be due to ischemia, neovascularization and/or diabetic macular edema, which are caused by breakdown of the blood-retina barrier at the level of the retinal pigment epithelium (RPE) and inner retinal vasculature. The prevalence of diabetes and its complications differ between Caucasian-Americans and certain minority populations, such as African-Americans and Asian-Americans. Individuals can be classified by their mitochondrial haplogroups, which are collections of single nucleotide polymorphisms (SNPs) in mitochondrial DNA (mtDNA) representing ancient geographic origins of populations. In this study, we compared the responses of diabetic human RPE cybrids, cell lines containing identical nuclei but mitochondria from either European (maternal European) or maternal African or Asian individuals, to hypoxia and high glucose levels. The African and Asian diabetic ([Afr+Asi]/DM) cybrids showed (1) resistance to both hyperglycemic and hypoxic stresses; (2) downregulation of pro-apoptotic indicator BAX; (3) upregulation of DNA methylation genes, such as DNMT3A and DNMT3B; and (4) resistance to DNA de-methylation by the methylation inhibitor 5-Aza-2’-deoxycytidine (5-Aza-dC) compared to European diabetic (Euro/DM) cybrids. Our findings suggest that mitochondria from African and Asian diabetic subjects possess a “metabolic memory” that confers resistance against hyperglycemia, hypoxia, and demethylation, and that this “metabolic memory” can be transferred into the RPE cybrid cell lines in vitro .
Author Atilano, Shari R.
Dolinko, Andrew H.
Chwa, Marilyn
Kenney, M. Cristina
AuthorAffiliation 2 Department of Ophthalmology, University of California Irvine, Irvine, California, 92697
1 Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, California, 92697
AuthorAffiliation_xml – name: 2 Department of Ophthalmology, University of California Irvine, Irvine, California, 92697
– name: 1 Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, California, 92697
Author_xml – sequence: 1
  givenname: Andrew H.
  surname: Dolinko
  fullname: Dolinko, Andrew H.
  organization: Department of Pathology and Laboratory Medicine, University of California Irvine, Department of Ophthalmology Research, Gavin Herbert Eye Institute, University of California Irvine
– sequence: 2
  givenname: Marilyn
  surname: Chwa
  fullname: Chwa, Marilyn
  organization: Department of Pathology and Laboratory Medicine, University of California Irvine
– sequence: 3
  givenname: Shari R.
  surname: Atilano
  fullname: Atilano, Shari R.
  organization: Department of Pathology and Laboratory Medicine, University of California Irvine
– sequence: 4
  givenname: M. Cristina
  orcidid: 0000-0003-1765-1750
  surname: Kenney
  fullname: Kenney, M. Cristina
  email: mkenney@uci.edu
  organization: Department of Pathology and Laboratory Medicine, University of California Irvine, Department of Ophthalmology Research, Gavin Herbert Eye Institute, University of California Irvine
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31811564$$D View this record in MEDLINE/PubMed
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Molecular Neurobiology is a copyright of Springer, (2019). All Rights Reserved.
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Thu Apr 24 23:07:52 EDT 2025
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Issue 3
Keywords Retinal pigment epithelial cells
African and Asian mitochondrial DNA haplogroups
Diabetic retinopathy (DR)
Cybrid cell model
Hyperglycemic and hypoxic stresses
Language English
License Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. http://www.springer.com/gb/open-access/authors-rights/aam-terms-v1
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AUTHOR CONTRIBUTIONS
Conceived and Designed Experiments – AHD, MCK, MC, SRA; Performed the Experiments – AHD, MC, SRA; Analyzed the Data – AHD, MCK, MC, SRA; Contributed reagents/Materials/Analysis tools – MCK; Wrote the Manuscript – AHD, MCK.
ORCID 0000-0003-1765-1750
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/7123578
PMID 31811564
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  year: 2020
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PublicationTitle Molecular neurobiology
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PublicationYear 2020
Publisher Springer US
Springer Nature B.V
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Snippet Diabetic retinopathy (DR) is the most common cause of blindness for individuals under the age of 65. This loss of vision can be due to ischemia,...
Diabetic retinopathy (DR) is the most common cause of blindness for individuals under the age of 65. This loss of vision can be due to ischemia,...
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StartPage 1636
SubjectTerms Adult
Aged
Apoptosis
Asian Americans
Asian People
Azacytidine
Biomedical and Life Sciences
Biomedicine
Blindness
Cell Biology
Cell lines
Cells, Cultured
Cybrids
Demethylation
Deoxyribonucleic acid
Diabetes
Diabetes mellitus
Diabetes Mellitus - metabolism
Diabetic retinopathy
Diabetic Retinopathy - genetics
DNA
DNA methylation
DNA, Mitochondrial - genetics
Edema
Epithelium
Female
Humans
Hyperglycemia
Hypoxia
Ischemia
Macular Edema - genetics
Male
Metabolism
Middle Aged
Mitochondria - metabolism
Mitochondrial DNA
Neurobiology
Neurology
Neurosciences
Polymorphism, Single Nucleotide - genetics
Population studies
Retina
Retinal pigment epithelium
Retinal Pigment Epithelium - cytology
Retinopathy
Signal Transduction - genetics
Single-nucleotide polymorphism
Vascularization
White People
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Title African and Asian Mitochondrial DNA Haplogroups Confer Resistance Against Diabetic Stresses on Retinal Pigment Epithelial Cybrid Cells In Vitro
URI https://link.springer.com/article/10.1007/s12035-019-01834-z
https://www.ncbi.nlm.nih.gov/pubmed/31811564
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https://pubmed.ncbi.nlm.nih.gov/PMC7123578
Volume 57
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