Inhibition of stress induced premature senescence in presenilin-1 mutated cells with water soluble Coenzyme Q10

Ma, Dennis; Stokes, Kyle; Mahngar, Kevinjeet; Domazet-Damjanov, Danijela; Sikorska, Marianna; Pandey, Siyaram

doi:10.1016/j.mito.2014.07.004

Cited by 30 publications

(42 citation statements)

References 39 publications

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“…The current study addressed the main mechanism of the protective effects of CoQ10 on cellular aging was that could decrease the oxidative stress [26, 60]. However, ROS, as a kind of signaling factor, are related with some intracellular pathways [31, 61, 62]; many of these signaling pathways are involved in regulation of cell senescence [63].…”

Section: Discussionmentioning

confidence: 99%

Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling

Zhang

Yan

et al. 2015

Oxidative Medicine and Cellular Longevity

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Increasing evidences indicate that reactive oxygen species are the main factor promoting stem cell aging. Recent studies have demonstrated that coenzyme Q10 (CoQ10) plays a positive role in organ and cellular aging. However, the potential for CoQ10 to protect stem cell aging has not been fully evaluated, and the mechanisms of cell senescence inhibited by CoQ10 are still poorly understood. Our previous study had indicated that D-galactose (D-gal) can remarkably induce mesenchymal stem cell (MSC) aging through promoting intracellular ROS generation. In this study, we showed that CoQ10 could significantly inhibit MSC aging induced by D-gal. Moreover, in the CoQ10 group, the expression of p-Akt and p-mTOR was clearly reduced compared with that in the D-gal group. However, after Akt activating by CA-Akt plasmid, the senescence-cell number in the CoQ10 group was significantly higher than that in the control group. These results indicated that CoQ10 could inhibit D-gal-induced MSC aging through the Akt/mTOR signaling.

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Section: Discussionmentioning

confidence: 99%

Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling

Zhang

Yan

et al. 2015

Oxidative Medicine and Cellular Longevity

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“…Cyto ID green dye specifically binds with autophagic vacuoles and fluoresces green. Mitochondria co-localizing with autophagic vacuoles appear yellow (vander Burgh et al, 2014; Ma et al, 2014). One x 10 5 cells were seeded onto uncoated 0.17 mm thick (25 mm diameter) clear delta T dishes (Bioptechs Inc, USA) and maintained under the same conditions as mentioned in the “Cell culture” section.…”

Section: Methodsmentioning

confidence: 99%

“…Cells were treated with CESP (100 μM) for 24 h. After the incubation, the cells were washed twice with media (room temperature) and incubated with 50 nM mitotracker red and one μl cyto ID dye in 500 μl of same media for 30 min in 5% CO 2 incubator at 37°C. The cells were then washed three times with PBS and examined by confocal laser scanning microscopy (Ma et al, 2014) (channel 488 and 570 for green and red respectively) (Carl Zeiss Microimaging). Mitochondrial morphology was assessed after staining with mitotracker red.…”

Section: Methodsmentioning

confidence: 99%

Mild mitochondrial metabolic deficits by α-ketoglutarate dehydrogenase inhibition cause prominent changes in intracellular autophagic signaling: Potential role in the pathobiology of Alzheimer's disease

Banerjee

Munshi

et al. 2016

Neurochemistry International

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Brain activities of the mitochondrial enzyme α-ketoglutarate dehydrogenase complex (KGDHC) are reduced in Alzheimer’s disease and other age-related neurodegenerative disorders. The goal of the present study was to test the consequences of mild impairment of KGDHC on the structure, protein signaling and dynamics (mitophagy, fusion, fission, biogenesis) of the mitochondria. Inhibition of KGDHC reduced its in situ activity by 23–53% in human neuroblastoma SH-SY5Y cells, but neither altered the mitochondrial membrane potential nor the ATP levels at any tested time-points. The attenuated KGDHC activity increased translocation of dynamin-related protein-1 (Drp1) and microtubule-associated protein 1A/1B-light chain 3 (LC3) from the cytosol to the mitochondria, and promoted mitochondrial cytochrome c release. Inhibition of KGDHC also increased the negative surface charges (anionic phospholipids as assessed by Annexin V binding) on the mitochondria. Morphological assessments of the mitochondria revealed increased fission and mitophagy. Taken together, our results suggest the existence of the regulation of the mitochondrial dynamism including fission and fusion by the mitochondrial KGDHC activity via the involvement of the cytosolic and mitochondrial protein signaling molecules. A better understanding of the link among mild impairment of metabolism, induction of mitophagy/autophagy and altered protein signaling will help to identify new mechanisms of neurodegeneration and reveal potential new therapeutic approaches.

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“…Previous work has shown a water-soluble formulation of Coenzyme Q 10 (Ubs-CoQ 10 ) to inhibit ROS production and protect against mitochondria-mediated apoptosis 29, 30 . Ubs-CoQ 10 was used and shown to reduce the percent of cells that underwent apoptosis by Compound A and I as indicated by the reduction in the Annexin V and PI apoptotic markers (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs

Pignanelli

Noel

et al. 2017

Sci Rep

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Recently, research has focused on targeting the oxidative and metabolic vulnerabilities in cancer cells. Natural compounds like curcumin that target such susceptibilities have failed further clinical advancements due to the poor stability and bioavailability as well as the need of high effective doses. We have synthesized and evaluated the anti-cancer activity of several monocarbonyl analogs of curcumin. Interestingly, two novel analogs (Compound A and I) in comparison to curcumin, have increased chemical stability and have greater anti-cancer activity in a variety of human cancer cells, including triple-negative, inflammatory breast cancer cells. In particular, the generation of reactive oxygen species was selective to cancer cells and occurred upstream of mitochondrial collapse and execution of apoptosis. Furthermore, Compound A in combination with another cancer-selective/pro-oxidant, piperlongumine, caused an enhanced anti-cancer effect. Most importantly, Compound A was well tolerated by mice and was effective in inhibiting the growth of human triple-negative breast cancer and leukemia xenografts in vivo when administered intraperitoneally. Thus, exploiting oxidative vulnerabilities in cancer cells could be a selective and efficacious means to eradicate malignant cells as demonstrated by the curcumin analogs presented in this report with high therapeutic potential.

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Inhibition of stress induced premature senescence in presenilin-1 mutated cells with water soluble Coenzyme Q10

Cited by 30 publications

References 39 publications

Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling

Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling

Mild mitochondrial metabolic deficits by α-ketoglutarate dehydrogenase inhibition cause prominent changes in intracellular autophagic signaling: Potential role in the pathobiology of Alzheimer's disease

Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs

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