Neurodegenerative Eye Disorders

Mohanty, Kuldeep; Dada, Rima; Dada, Tanuj

doi:10.1097/apo.0000000000000203

Cited by 8 publications

(1 citation statement)

References 84 publications

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“…Among the MIEH individuals, there was a high mutation frequency and density in mtDNA m.8584G > A and m.8701A > G mutations. Specifically, an amino acid change at the m.8414C > T in the ATP8 gene (leucine to phenylalanine) shows that mtDNA variants may be able to affect the development of hypertension in China [ 35 ]. Ancestral variants of mtDNA define population-specific mtDNA lineages or haplogroups.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA 7908–8816 region mutations in maternally inherited essential hypertensive subjects in China

Zhu

2018

BMC Med Genomics

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BackgroundNuclear genes or family-based mitochondrial screening have been the focus of genetic studies into essential hypertension. Studies into the role of mitochondria in sporadic Chinese hypertensives are lacking. The objective of the study was to explore the relationship between mitochondrial DNA (mtDNA) variations and the development of maternally inherited essential hypertension (MIEH) in China.MethodsYangzhou residents who were outpatients or in-patients at the Department of Cardiology in Northern Jiangsu People’s Hospital (Jiangsu, China) from June 2009 to June 2015 were recruited in a 1:1 case control study of 600 gender-matched Chinese MIEH subjects and controls. Genomic DNA was isolated from whole blood cells. The most likely sites for hypertension were screened using oligodeoxynucleotides at positions 7908–8816, purified and subsequently analyzed by direct sequencing according to the revised consensus Cambridge sequence. The frequency, density, type and conservative evolution of mtDNA variations were comprehensively analyzed.ResultsWe found a statistical difference between the two groups for body mass index, waist circumference, abdominal circumference, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, uric acid, creatinine and blood urea nitrogen (P < 0.05). More amino-acid changes and RNA variants were found in MIEH subjects than the controls (P < 0.01). The detection system simultaneously identified 40 different heteroplasmic or homoplasmic mutations in 4 genes: COXII, tRNALys, ATP8 and ATP 6. The mtDNA variations were mainly distributed in regions of ATP6 binding sites, and the site of highest mutation frequency was m. 8414C > T. Three changes in single bases (C8414T in ATP8, A8701G in ATP6 and G8584A in ATP6) were significantly different in the MIEH patients and the controls (P < 0.001). The m.8273_8281del mutation was identified from 59 MIEH patients.ConclusionsOur results indicate that novel mtDNA mutations may be involved in the pathological process of MIEH, and mitochondrial genetic characteristics were identified in MIEH individuals.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0408-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA 7908–8816 region mutations in maternally inherited essential hypertensive subjects in China

Zhu

2018

BMC Med Genomics

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Effects of collagen cross-linking on the keratoconus metabolic network

Sharif

Sejersen

Frank

et al. 2018

Eye

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Indomethacin impairs mitochondrial dynamics by activating the PKCζ–p38–DRP1 pathway and inducing apoptosis in gastric cancer and normal mucosal cells

Mazumder

Debsharma

et al. 2019

Journal of Biological Chemistry

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The subcellular mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in gastric cancer and normal mucosal cells is elusive because of the diverse cyclooxygenase-independent effects of these drugs. Using human gastric carcinoma cells (AGSs) and a rat gastric injury model, here we report that the NSAID indomethacin activates the protein kinase Cζ (PKCζ)–p38 MAPK (p38)–dynamin-related protein 1 (DRP1) pathway and thereby disrupts the physiological balance of mitochondrial dynamics by promoting mitochondrial hyper-fission and dysfunction leading to apoptosis. Notably, DRP1 knockdown or SB203580-induced p38 inhibition reduced indomethacin-induced damage to AGSs. Indomethacin impaired mitochondrial dynamics by promoting fissogenic activation and mitochondrial recruitment of DRP1 and down-regulating fusogenic optic atrophy 1 (OPA1) and mitofusins in rat gastric mucosa. Consistent with OPA1 maintaining cristae architecture, its down-regulation resulted in EM-detectable cristae deformity. Deregulated mitochondrial dynamics resulting in defective mitochondria were evident from enhanced Parkin expression and mitochondrial proteome ubiquitination. Indomethacin ultimately induced mitochondrial metabolic and bioenergetic crises in the rat stomach, indicated by compromised fatty acid oxidation, reduced complex I– associated electron transport chain activity, and ATP depletion. Interestingly, Mdivi-1, a fission-preventing mito-protective drug, reversed indomethacin-induced DRP1 phosphorylation on Ser-616, mitochondrial proteome ubiquitination, and mitochondrial metabolic crisis. Mdivi-1 also prevented indomethacin-induced mitochondrial macromolecular damage, caspase activation, mucosal inflammation, and gastric mucosal injury. Our results identify mitochondrial hyper-fission as a critical and common subcellular event triggered by indomethacin that promotes apoptosis in both gastric cancer and normal mucosal cells, thereby contributing to mucosal injury.

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Neurodegenerative Eye Disorders

Cited by 8 publications

References 84 publications

Mitochondrial DNA 7908–8816 region mutations in maternally inherited essential hypertensive subjects in China

Mitochondrial DNA 7908–8816 region mutations in maternally inherited essential hypertensive subjects in China

Effects of collagen cross-linking on the keratoconus metabolic network

Indomethacin impairs mitochondrial dynamics by activating the PKCζ–p38–DRP1 pathway and inducing apoptosis in gastric cancer and normal mucosal cells

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