MKK3 as oncotarget

Bossi, Gianluca

doi:10.18632/aging.100878

Cited by 21 publications

(37 citation statements)

References 7 publications

(12 reference statements)

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“…At term, oxidative stress and inflammation build up in the amniotic cavity, causing cellular senescence of the fetal membranes and subsequent release of signals of cellular damage (Menon, 2014; Behnia et al, 2015, 2016; Polettini et al, 2015; Menon et al, 2016b). Senescent signal action is primarily localized, although we have shown signals of cellular damage are also packaged into exosomes from AECs treated with the oxidative stress inducer cigarette smoke extract (Sheller et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Feto-Maternal Trafficking of Exosomes in Murine Pregnancy Models

et al. 2016

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Timing and initiation of labor are well-orchestrated by signals communicated between the fetal and maternal compartments; however, how these signals are communicated is not completely understood. Fetal exosomes, intercellular signaling vesicles, may play a key role in the process. The objective of this study was to evaluate exosome trafficking in vivo from fetal to maternal compartments. Pregnant CD-1 mice were intra-amniotically injected on gestational day 16 and 17 with exosomes isolated from primary human amnion epithelial cells fluorescently labeled with the lipophilic dye 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR). All our analyses were performed on samples collected on Day 18. After 24 h, mice were imaged using Bruker MS FX PRO In vivo Imager and tissues were collected. In vivo imaging of mouse showed fluorescence in the uterus, on the exosome-injected side whereas the uterine tissues from the uninjected side and saline and dye alone injected animals remained negative. Histological analysis of placenta showed exosome migration from the fetal to the maternal side of the placenta. Fluorescence released from exosomes was seen in maternal blood samples as well as in maternal uterus and kidneys. This study demonstrates that exosomal cargo can be carried through systemic route from the fetal to the maternal side of the uterine tissues during pregnancy, supporting the idea that fetal signals can be delivered via exosomes.

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Section: Discussionmentioning

confidence: 99%

Feto-Maternal Trafficking of Exosomes in Murine Pregnancy Models

et al. 2016

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“… 4 This DNAm age metric has been shown to be one of the most accurate biological measures of chronological age reported to date. 4 Importantly, investigators have now documented discrepancies between DNAm age and chronological age, referred to as epigenetic age acceleration, as predictive of all-cause mortality 6 , 7 , 8 , 9 and associated with both stress exposure and the development of psychiatric disorders such as post-traumatic stress disorder (PTSD). 10 , 11 , 12 These findings indicate that accelerated epigenetic age may be a biomarker of changes in stress-related cellular functioning.…”

Section: Introductionmentioning

confidence: 99%

Accelerated DNA methylation age in adolescent girls: associations with elevated diurnal cortisol and reduced hippocampal volume

et al. 2017

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Numerous studies have linked exposure to stress to adverse health outcomes through the effects of cortisol, a product of the stress response system, on cellular aging processes. Accelerated DNA methylation age is a promising epigenetic marker associated with stress and disease risk that may constitute a link from stress response to changes in neural structures. Specifically, elevated glucocorticoid signaling likely contributes to accelerating DNA methylation age, which may signify a maladaptive stress-related cascade that leads to hippocampal atrophy. We examined the relations among diurnal cortisol levels, DNA methylation age and hippocampal volume in a longitudinal study of 46 adolescent girls. We computed area under the curve from two daily cortisol collection periods, and calculated DNA methylation age using previously established methods based on a set of CpG sites associated with chronological age. We computed a residual score by partialling out chronological age; higher discrepancies reflect relatively accelerated DNA methylation age. We assessed hippocampal volume via T1-weighted images and automated volumetric segmentation. We found that greater diurnal cortisol production was associated with accelerated DNA methylation age, which in turn was associated with reduced left hippocampal volume. Finally, accelerated DNA methylation age significantly mediated the association between diurnal cortisol and left hippocampal volume. Thus, accelerated DNA methylation age may be an epigenetic marker linking hypothalamic–pituitary–adrenal axis dysregulation with neural structure. If these findings are replicated, the current study provides a method for advancing our understanding of mechanisms by which glucocorticoid signaling is associated with cellular aging and brain development.

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“…These sORFS corresponded with small mitochondria-derived peptides (MDPs). The first MDP, humanin, was discovered in 2001 by Hashimoto et al ( 78 ), followed by the discovery of MOTS-c by Lee et al in 2015 ( 79 ) and small humanin-like peptides (SHLP 1–6) by Cobb et al in 2016 ( 80 ). Emerging evidence suggests that MDPs play important roles in the regulation of cellular bioenergetics and system metabolism by modulating insulin sensitivity and glucose homeostasis [reviewed by Kim et al ( 81 )], but whether these hormone-like peptides are bona fide retrograde signaling molecules that modulate nuclear gene expression or induce epigenetic changes intracellularly or in other cells remains to be determined.…”

Section: Mito-nuclear Cross Talkmentioning

confidence: 99%

Functional Mitochondria in Health and Disease

et al. 2017

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The ability to rapidly adapt cellular bioenergetic capabilities to meet rapidly changing environmental conditions is mandatory for normal cellular function and for cancer progression. Any loss of this adaptive response has the potential to compromise cellular function and render the cell more susceptible to external stressors such as oxidative stress, radiation, chemotherapeutic drugs, and hypoxia. Mitochondria play a vital role in bioenergetic and biosynthetic pathways and can rapidly adjust to meet the metabolic needs of the cell. Increased demand is met by mitochondrial biogenesis and fusion of individual mitochondria into dynamic networks, whereas a decrease in demand results in the removal of superfluous mitochondria through fission and mitophagy. Effective communication between nucleus and mitochondria (mito-nuclear cross talk), involving the generation of different mitochondrial stress signals as well as the nuclear stress response pathways to deal with these stressors, maintains bioenergetic homeostasis under most conditions. However, when mitochondrial DNA (mtDNA) mutations accumulate and mito-nuclear cross talk falters, mitochondria fail to deliver critical functional outputs. Mutations in mtDNA have been implicated in neuromuscular and neurodegenerative mitochondriopathies and complex diseases such as diabetes, cardiovascular diseases, gastrointestinal disorders, skin disorders, aging, and cancer. In some cases, drastic measures such as acquisition of new mitochondria from donor cells occurs to ensure cell survival. This review starts with a brief discussion of the evolutionary origin of mitochondria and summarizes how mutations in mtDNA lead to mitochondriopathies and other degenerative diseases. Mito-nuclear cross talk, including various stress signals generated by mitochondria and corresponding stress response pathways activated by the nucleus are summarized. We also introduce and discuss a small family of recently discovered hormone-like mitopeptides that modulate body metabolism. Under conditions of severe mitochondrial stress, mitochondria have been shown to traffic between cells, replacing mitochondria in cells with damaged and malfunctional mtDNA. Understanding the processes involved in cellular bioenergetics and metabolic adaptation has the potential to generate new knowledge that will lead to improved treatment of many of the metabolic, degenerative, and age-related inflammatory diseases that characterize modern societies.

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MKK3 as oncotarget

Cited by 21 publications

References 7 publications

Feto-Maternal Trafficking of Exosomes in Murine Pregnancy Models

Feto-Maternal Trafficking of Exosomes in Murine Pregnancy Models

Accelerated DNA methylation age in adolescent girls: associations with elevated diurnal cortisol and reduced hippocampal volume

Functional Mitochondria in Health and Disease

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