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Proteome analysis of monocytes implicates altered mitochondrial biology in adults reporting adverse childhood experiences.

ABSTRACT: The experience of adversity in childhood has been associated with poor health outcomes in adulthood. In search of the biological mechanisms underlying these effects, research so far focused on alterations of DNA methylation or shifts in transcriptomic profiles. The level of protein, however, has been largely neglected. We utilized mass spectrometry to investigate the proteome of CD14⁺ monocytes in healthy adults reporting childhood adversity and a control group before and after psychosocial stress exposure. Particular proteins involved in (i) immune processes, such as neutrophil-related proteins, (ii) protein metabolism, or (iii) proteins related to mitochondrial biology, such as those involved in energy production processes, were upregulated in participants reporting exposure to adversity in childhood. This functional triad was further corroborated by protein interaction- and co-expression analyses, was independent of stress exposure, i.e. observed at both pre- and post-stress time points, and became evident especially in females. In line with the mitochondrial allostatic load model, our findings provide evidence for the long-term effects of childhood adversity on mitochondrial biology.

SUBMITTER: Zang JCS

PROVIDER: S-EPMC9889346 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Proteome analysis of monocytes implicates altered mitochondrial biology in adults reporting adverse childhood experiences.

Zang Johannes C S JCS May Caroline C Hellwig Birte B Moser Dirk D Hengstler Jan G JG Cole Steve S Heinrichs Markus M Rahnenführer Jörg J Marcus Katrin K Kumsta Robert R

Translational psychiatry 20230201 1

The experience of adversity in childhood has been associated with poor health outcomes in adulthood. In search of the biological mechanisms underlying these effects, research so far focused on alterations of DNA methylation or shifts in transcriptomic profiles. The level of protein, however, has been largely neglected. We utilized mass spectrometry to investigate the proteome of CD14<sup>+</sup> monocytes in healthy adults reporting childhood adversity and a control group before and after psycho ...[more]

PMID: 36720844

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Project description:Adverse childhood experiences (ACEs) are traumatic events during childhood known to affect health and well-being across the life span. The detrimental impact ACEs have on children and young people is well-established. It is also known that 85 to 90% of children have at least one sibling. Using this as the foundation for our inquiry, the purpose of this scoping review was to understand what we currently know about the experiences of siblings living with ACEs. Sibling relationships are unique, and for some the most enduring of experiences. These relationships can be thought of as bonds held together by love and warmth; however, they can also provide scope for undesirable outcomes, such as escalation of conflicts and animosities. This scoping review was conducted following Arksey and O'Malley's (2005) methodological framework, complemented by the PAGER framework (Bradbury-Jones et al. 2021), offering a structured approach to the review's analysis and reporting through presenting the Patterns, Advances, Gaps, and Evidence for practice and Research. In June 2020, we searched 12 databases, with 11,469 results. Articles were screened for eligibility by the review team leaving a total of 148 articles meeting the inclusion criteria. Included articles highlighted overwhelming evidence of older siblings shielding younger siblings, and the likelihood that when one sibling experiences adversity, other siblings will be experiencing it themselves or vicariously. The implications of this in practice are that support services and statutory bodies need to ensure considerations are given to all siblings when one has presented with experiencing childhood adversity, especially to older siblings who may take far more burden as regards care-giving and protection of younger siblings. Given that more than half of the included articles did not offer any theoretical understanding to sibling experiences of ACEs, this area is of importance for future research. Greater attention is also needed for research exploring different types of sibling relationships (full, step, half), and whether these influence the impact that ACEs have on children and young people.

Project description:Myocardial ischemia-reperfusion induces mitochondrial dysfunction and, depending upon the degree of injury, may lead to cardiac cell death. However, our ability to understand mitochondrial dysfunction has been hindered by an absence of molecular markers defining the various degrees of injury. To address this paucity of knowledge, we sought to characterize the impact of ischemic damage on mitochondrial proteome biology. We hypothesized that ischemic injury induces differential alterations in various mitochondrial subcompartments, that these proteomic changes are specific to the severity of injury, and that they are important to subsequent cellular adaptations to myocardial ischemic injury. Accordingly, an in vitro model of cardiac mitochondria injury in mice was established to examine two stress conditions: reversible injury (induced by mild calcium overload) and irreversible injury (induced by hypotonic stimuli). Both forms of injury had a drastic impact on the proteome biology of cardiac mitochondria. Altered mitochondrial function was concomitant with significant protein loss/shedding from the injured organelles. In the setting of mild calcium overload, mitochondria retained functionality despite the release of numerous proteins, and the majority of mitochondria remained intact. In contrast, hypotonic stimuli caused severe damage to mitochondrial structure and function, induced increased oxidative modification of mitochondrial proteins, and brought about detrimental changes to the subproteomes of the inner mitochondrial membrane and matrix. Using an established in vivo murine model of regional myocardial ischemic injury, we validated key observations made by the in vitro model. This preclinical investigation provides function and suborganelle location information on a repertoire of cardiac mitochondrial proteins sensitive to ischemia reperfusion stress and highlights protein clusters potentially involved in mitochondrial dysfunction in the setting of ischemic injury.

Project description:IntroductionAlternative measurement approaches for adverse childhood experiences (i.e., count score versus individual adverse childhood experiences measured dichotomously versus individual adverse childhood experiences measured ordinally) can alter the association between adverse childhood experiences and adverse outcomes. This could significantly impact the interpretation of adverse childhood experiences research.MethodsData were collected in 2018 (analyzed in 2020) via Amazon's Mechanical Turk and from people incarcerated in 4 correctional facilities (N=1,451). Included adverse childhood experience questions measured the following: physical, emotional, and sexual abuse; physical and emotional neglect; household mental illness, substance use, domestic violence, and incarceration; and exposure to community violence before age 18 years. A total of 19 measured outcomes spanned 4 domains of functioning: general functioning, substance use, psychopathology, and criminal behavior.ResultsRegression models using the count score explained the least amount of variance in outcomes, whereas multivariable regression models assessing adverse childhood experiences on a continuum explained the most variance. In many instances, the explained variance increased by 2-5 times across the predictive models. When comparing regression coefficients for multivariable regression models that measured adverse childhood experiences as binary versus ordinal, there were notable differences in the effect sizes and in which adverse childhood experiences predicted outcomes. Disparities in results were most pronounced among high-risk populations that experience a disproportionate amount of adverse childhood experiences.ConclusionsAlternative methods of measuring adverse childhood experiences can influence understanding of their true impact. These findings suggest that the deleterious effects of imprecise measurement methods may be most pronounced in the populations most at risk of adverse childhood experiences. For the sake of prevention, the measurement of adverse childhood experiences must evolve.

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Proteome analysis of monocytes implicates altered mitochondrial biology in adults reporting adverse childhood experiences.

Publications

Proteome analysis of monocytes implicates altered mitochondrial biology in adults reporting adverse childhood experiences.

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