Intracellular and extracellular factors influencing the genotoxicity of nitric oxide and reactive oxygen species

Kim, Min Young

doi:10.3892/ol.2017.5584

Cited by 11 publications

(7 citation statements)

References 46 publications

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“…Extracellular factors and the regulation of mitochondrial function and oxidative stress have been demonstrated to support the survival of various cell types (Hasan et al, 2003; Echave et al, 2009; Li et al, 2009; Wang et al, 2013; Genis et al, 2014; Pyakurel et al, 2015; Kim, 2017). For cells that do not have a capacity for regeneration, like hair cells, the regulation of these factors and intracellular processes are particularly important.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-associated plasma protein-aa supports hair cell survival by regulating mitochondrial function

Alassaf

Daykin

Mathiaparanam

et al. 2019

eLife

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To support cell survival, mitochondria must balance energy production with oxidative stress. Inner ear hair cells are particularly vulnerable to oxidative stress; thus require tight mitochondrial regulation. We identified a novel molecular regulator of the hair cells’ mitochondria and survival: Pregnancy-associated plasma protein-aa (Pappaa). Hair cells in zebrafish pappaa mutants exhibit mitochondrial defects, including elevated mitochondrial calcium, transmembrane potential, and reactive oxygen species (ROS) production and reduced antioxidant expression. In pappaa mutants, hair cell death is enhanced by stimulation of mitochondrial calcium or ROS production and suppressed by a mitochondrial ROS scavenger. As a secreted metalloprotease, Pappaa stimulates extracellular insulin-like growth factor 1 (IGF1) bioavailability. We found that the pappaa mutants’ enhanced hair cell loss can be suppressed by stimulation of IGF1 availability and that Pappaa-IGF1 signaling acts post-developmentally to support hair cell survival. These results reveal Pappaa as an extracellular regulator of hair cell survival and essential mitochondrial function.

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Section: Discussionmentioning

confidence: 99%

Pregnancy-associated plasma protein-aa supports hair cell survival by regulating mitochondrial function

Alassaf

Daykin

Mathiaparanam

et al. 2019

eLife

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“…Being aware of these data, we analyzed oxidative damage to genetic material. Oxidative DNA/RNA damage is reflected in nucleobase oxidation, mainly guanine and/or chromosomal abnormalities [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Chromosomal Aberrations and Oxidative Stress in Psoriatic Patients with and without Metabolic Syndrome

et al. 2022

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Psoriasis and metabolic syndrome (MetS), a common comorbidity of psoriasis, are associated with mild chronic systemic inflammation that increases oxidative stress and causes cell and tissue damage. At the cellular level, chromosomal and DNA damage has been documented, thus confirming their genotoxic effect. The main objective of our study was to show the genotoxic potential of chronic inflammation and determine whether the presence of both pathologies increases chromosomal damage compared to psoriasis alone and to evaluate whether there are correlations between selected parameters and chromosomal aberrations in patients with psoriasis and MetS psoriasis. Clinical examination (PASI score and MetS diagnostics according to National Cholesterol Education Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults; NCE/ATPIII criteria), biochemical analysis of blood samples (fasting glucose, total cholesterol, low density and high density lipoproteins; LDL, HDL, non-HDL, and triglycerides;TAG), DNA/RNA oxidative damage, and chromosomal aberration test were performed in 41 participants (20 patients with psoriasis without MetS and 21 with MetS and psoriasis). Our results showed that patients with psoriasis without metabolic syndrome (nonMetS) and psoriasis and MetS had a higher rate of chromosomal aberrations than the healthy population for which the limit of spontaneous, natural aberration was <2%. No significant differences in the aberration rate were found between the groups. However, a higher aberration rate (higher than 10%) and four numerical aberrations were documented only in the MetS group. We found no correlations between the number of chromosomal aberrations and the parameters tested except for the correlation between aberrations and HDL levels in nonMetS patients (rho 0.44; p < 0.02). Interestingly, in the MetS group, a higher number of chromosomal aberrations was documented in non-smokers compared to smokers. Data from our current study revealed an increased number of chromosomal aberrations in patients with psoriasis and MetS compared to the healthy population, especially in psoriasis with MetS, which could increase the genotoxic effect of inflammation and the risk of genomic instability, thus increasing the risk of carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Pregnancy-associated plasma protein-aa supports hair cell survival by regulating mitochondrial function

Alassaf

Daykin

Mathiaparanam

et al. 2019

Preprint

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19To support cell survival, mitochondria must balance energy production with oxidative stress. Inner 20 ear hair cells are particularly vulnerable to oxidative stress; thus require tight mitochondrial regulation. 21 We identified a novel molecular regulator of the hair cells' mitochondria and survival: Pregnancy-22 associated plasma protein-aa (Pappaa). Hair cells in zebrafish pappaa mutants exhibit mitochondrial 23 defects, including elevated mitochondrial calcium, transmembrane potential, and reactive oxygen 24 species (ROS) production and reduced antioxidant expression. In pappaa mutants, hair cell death is 25 enhanced by stimulation of mitochondrial calcium or ROS production and suppressed by a 26 mitochondrial ROS scavenger. As a secreted metalloprotease, Pappaa stimulates extracellular insulin-27 like growth factor 1 (IGF1) bioavailability. We found that the pappaa mutants' enhanced hair cell loss 28 can be suppressed by stimulation of IGF1 availability and that Pappaa-IGF1 signaling acts post-29 developmentally to support hair cell survival. These results reveal Pappaa as an extracellular regulator 30 of hair cell survival and essential mitochondrial function. 31 32Without a sufficient regenerative capacity, a nervous system's form and function critically depends 33 on the molecular and cellular mechanisms that support its cells' longevity. Neural cell survival is 34 inherently challenged by the nervous system's high energy demand, which is required to support basic 35 functions, including maintaining membrane potential, propagating electrical signals, and coordinating 36 the release and uptake of neurotransmitters (Halliwell, 2006; Kann and Kovács, 2007; Howarth et al., 37 2012). Metabolic energy is primarily supplied by mitochondrial oxidative phosphorylation (Kann and 38 Kovács, 2007). Although this process is essential to cell survival, a cytotoxic consequence is the 39 generation of reactive oxygen species (ROS). Oxidative stress caused by ROS accumulation damages 40 vital cell components including DNA, proteins, and lipids (Schieber and Chandel, 2014). Neural cells 41 are particularly vulnerable to oxidative stress due not only to their energy demand and thereby ROS 42 production, but also to their relatively insufficient antioxidant capacity (Halliwell, 1992). This 43 heightened susceptibility to oxidative stress-mediated cell death is believed to underlie aging and 44 neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and 45 Amyotrophic lateral sclerosis (ALS) (Perry et al., 2002; Barber et al., 2006; Mattson and Magnus, 46 2006; Blesa et al., 2015). 47 Hair cells of the inner ear are a population of neural cells that are particularly susceptible to 48 oxidative stress-induced death (Gonzalez-Gonzalez, 2017) These specialized sensory cells relay sound 49 and balance information to the central nervous system. Hair cell death or damage, which is irreversible 50 in mammals, is the primary cause of hearing loss, and is exacerbated by ag...

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Intracellular and extracellular factors influencing the genotoxicity of nitric oxide and reactive oxygen species

Cited by 11 publications

References 46 publications

Pregnancy-associated plasma protein-aa supports hair cell survival by regulating mitochondrial function

Pregnancy-associated plasma protein-aa supports hair cell survival by regulating mitochondrial function

Chromosomal Aberrations and Oxidative Stress in Psoriatic Patients with and without Metabolic Syndrome

Pregnancy-associated plasma protein-aa supports hair cell survival by regulating mitochondrial function

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