Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3 Article Swipe
Iswariyaraja Sridevi Gurubaran
,
Hanna Heloterä
,
Stephen Marry
,
Ali Koskela
,
Juha M. T. Hyttinen
,
Jussi J. Paterno
,
Arto Urtti
,
Mei Chen
,
Heping Xu
,
Anu Kauppinen
,
Kai Kaarniranta
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/biology10070622
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/biology10070622
Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation.
Related Topics
Concepts
Biology
Oxidative stress
Inflammation
C5a receptor
Receptor
Cell biology
Complement factor B
Complement factor I
Downregulation and upregulation
Endocrinology
Internal medicine
Complement system
Immunology
Biochemistry
Antibody
Medicine
Gene
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/biology10070622
- https://www.mdpi.com/2079-7737/10/7/622/pdf?version=1625563079
- OA Status
- gold
- Cited By
- 10
- References
- 101
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3180432640
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3180432640Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/biology10070622Digital Object Identifier
- Title
-
Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3Work title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2021Year of publication
- Publication date
-
2021-07-04Full publication date if available
- Authors
-
Iswariyaraja Sridevi Gurubaran, Hanna Heloterä, Stephen Marry, Ali Koskela, Juha M. T. Hyttinen, Jussi J. Paterno, Arto Urtti, Mei Chen, Heping Xu, Anu Kauppinen, Kai KaarnirantaList of authors in order
- Landing page
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https://doi.org/10.3390/biology10070622Publisher landing page
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https://www.mdpi.com/2079-7737/10/7/622/pdf?version=1625563079Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
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https://www.mdpi.com/2079-7737/10/7/622/pdf?version=1625563079Direct OA link when available
- Concepts
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Biology, Oxidative stress, Inflammation, C5a receptor, Receptor, Cell biology, Complement factor B, Complement factor I, Downregulation and upregulation, Endocrinology, Internal medicine, Complement system, Immunology, Biochemistry, Antibody, Medicine, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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10Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 3, 2023: 2, 2022: 3Per-year citation counts (last 5 years)
- References (count)
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101Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.to | 8, 111, 132, 206, 214 |
| abstract_inverted_index.we | 20, 71, 141 |
| abstract_inverted_index.C3, | 130 |
| abstract_inverted_index.C3. | 160 |
| abstract_inverted_index.C5a | 126 |
| abstract_inverted_index.Our | 183 |
| abstract_inverted_index.and | 4, 35, 56, 94, 172, 188, 218 |
| abstract_inverted_index.are | 6 |
| abstract_inverted_index.dKO | 81, 106, 181 |
| abstract_inverted_index.dry | 25, 198 |
| abstract_inverted_index.end | 177 |
| abstract_inverted_index.for | 174 |
| abstract_inverted_index.the | 22, 36, 43, 73, 153, 203 |
| abstract_inverted_index.was | 149 |
| abstract_inverted_index.C5a, | 157 |
| abstract_inverted_index.also | 162 |
| abstract_inverted_index.data | 185 |
| abstract_inverted_index.main | 184 |
| abstract_inverted_index.show | 186 |
| abstract_inverted_index.such | 28 |
| abstract_inverted_index.that | 143 |
| abstract_inverted_index.this | 197 |
| abstract_inverted_index.type | 113 |
| abstract_inverted_index.were | 102 |
| abstract_inverted_index.wild | 112 |
| abstract_inverted_index.with | 192 |
| abstract_inverted_index.(RPE) | 47 |
| abstract_inverted_index.(dKO) | 67 |
| abstract_inverted_index.Here, | 70 |
| abstract_inverted_index.acute | 168 |
| abstract_inverted_index.cells | 48 |
| abstract_inverted_index.e.g., | 14 |
| abstract_inverted_index.found | 142 |
| abstract_inverted_index.gamma | 61 |
| abstract_inverted_index.known | 7 |
| abstract_inverted_index.mice. | 82 |
| abstract_inverted_index.mount | 207 |
| abstract_inverted_index.mouse | 68 |
| abstract_inverted_index.phase | 169 |
| abstract_inverted_index.those | 97 |
| abstract_inverted_index.trend | 119 |
| abstract_inverted_index.while | 96, 212 |
| abstract_inverted_index.(AMD). | 18 |
| abstract_inverted_index.double | 65 |
| abstract_inverted_index.factor | 51, 54, 138 |
| abstract_inverted_index.levels | 89, 195 |
| abstract_inverted_index.model. | 69, 200 |
| abstract_inverted_index.retina | 204 |
| abstract_inverted_index.serine | 146 |
| abstract_inverted_index.showed | 117 |
| abstract_inverted_index.signs, | 27 |
| abstract_inverted_index.stress | 3 |
| abstract_inverted_index.tissue | 216 |
| abstract_inverted_index.1-alpha | 63 |
| abstract_inverted_index.Further | 115 |
| abstract_inverted_index.chronic | 1 |
| abstract_inverted_index.enzyme, | 148 |
| abstract_inverted_index.macular | 16 |
| abstract_inverted_index.markers | 77 |
| abstract_inverted_index.nuclear | 50 |
| abstract_inverted_index.pathway | 155 |
| abstract_inverted_index.pigment | 45 |
| abstract_inverted_index.primary | 167 |
| abstract_inverted_index.protein | 171 |
| abstract_inverted_index.resolve | 219 |
| abstract_inverted_index.retina. | 182 |
| abstract_inverted_index.retinal | 44, 107 |
| abstract_inverted_index.stress, | 32 |
| abstract_inverted_index.strives | 205 |
| abstract_inverted_index.tightly | 134 |
| abstract_inverted_index.towards | 120 |
| abstract_inverted_index.various | 12 |
| abstract_inverted_index.AMD-like | 26, 199 |
| abstract_inverted_index.NOD-like | 99 |
| abstract_inverted_index.advanced | 175 |
| abstract_inverted_index.analysis | 84, 116 |
| abstract_inverted_index.animals. | 114 |
| abstract_inverted_index.compared | 110 |
| abstract_inverted_index.detected | 163 |
| abstract_inverted_index.dynamics | 74 |
| abstract_inverted_index.elevated | 30 |
| abstract_inverted_index.general, | 202 |
| abstract_inverted_index.increase | 87, 122, 165 |
| abstract_inverted_index.involved | 10, 150 |
| abstract_inverted_index.knockout | 66 |
| abstract_inverted_index.maintain | 215 |
| abstract_inverted_index.observed | 131 |
| abstract_inverted_index.oxidized | 40 |
| abstract_inverted_index.presence | 23 |
| abstract_inverted_index.products | 178 |
| abstract_inverted_index.protease | 147 |
| abstract_inverted_index.receptor | 60, 100, 173 |
| abstract_inverted_index.reported | 21 |
| abstract_inverted_index.response | 211 |
| abstract_inverted_index.revealed | 85 |
| abstract_inverted_index.terminal | 154 |
| abstract_inverted_index.thrombin | 189 |
| abstract_inverted_index.together | 191 |
| abstract_inverted_index.2-related | 53 |
| abstract_inverted_index.Toll-like | 91 |
| abstract_inverted_index.component | 125, 129 |
| abstract_inverted_index.decreased | 103, 193 |
| abstract_inverted_index.diseases, | 13 |
| abstract_inverted_index.enhancing | 152 |
| abstract_inverted_index.erythroid | 52 |
| abstract_inverted_index.glycation | 176 |
| abstract_inverted_index.materials | 41 |
| abstract_inverted_index.mitophagy | 34 |
| abstract_inverted_index.oxidative | 2, 31 |
| abstract_inverted_index.producing | 156 |
| abstract_inverted_index.receptors | 92 |
| abstract_inverted_index.regulated | 135 |
| abstract_inverted_index.specimens | 108 |
| abstract_inverted_index.thrombin, | 144 |
| abstract_inverted_index.C-reactive | 170 |
| abstract_inverted_index.attempting | 213 |
| abstract_inverted_index.complement | 124, 137 |
| abstract_inverted_index.epithelial | 46 |
| abstract_inverted_index.peroxisome | 58 |
| abstract_inverted_index.Previously, | 19 |
| abstract_inverted_index.age-related | 15 |
| abstract_inverted_index.coactivator | 62 |
| abstract_inverted_index.detrimental | 39 |
| abstract_inverted_index.homeostasis | 217 |
| abstract_inverted_index.independent | 127, 158 |
| abstract_inverted_index.accumulation | 37 |
| abstract_inverted_index.degeneration | 17 |
| abstract_inverted_index.inflammation | 5 |
| abstract_inverted_index.inflammatory | 76, 210 |
| abstract_inverted_index.investigated | 72 |
| abstract_inverted_index.one-year-old | 79 |
| abstract_inverted_index.orchestrated | 209 |
| abstract_inverted_index.upregulation | 190 |
| abstract_inverted_index.NFE2L2/PGC1α | 80, 105, 180 |
| abstract_inverted_index.dysfunctional | 33 |
| abstract_inverted_index.inflammation. | 220 |
| abstract_inverted_index.Interestingly, | 140 |
| abstract_inverted_index.(NFE2L2/PGC1α) | 64 |
| abstract_inverted_index.Aging-associated | 0 |
| abstract_inverted_index.Immunohistochemical | 83 |
| abstract_inverted_index.proliferator-activated | 59 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 94 |
| corresponding_author_ids | https://openalex.org/A5021448617 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 11 |
| corresponding_institution_ids | https://openalex.org/I175532246, https://openalex.org/I4210092991 |
| citation_normalized_percentile.value | 0.81242818 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |