Metallothionein 2A affects the cell respiration by suppressing the expression of mitochondrial protein cytochrome c oxidase subunit II

Bragina, Olga; Gurjanova, Karina; Krishtal, Jekaterina; Kulp, Maria; Karro, Niina; Tõugu, Vello; Palumaa, Peep

doi:10.1007/s10863-015-9609-9

Cited by 14 publications

(14 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This up-regulation in fibrotic transcripts is in agreement with our observed adipocyte hypertrophy, as discussed previously [ 17 ], and is associated with increased local inflammation [ 22 , 23 ]. Metallothionein 2A was increased ∼350%; its increase in human embryonic kidney (HEK) cells has been associated with a reduced level of cytochrome c oxidase subunit II protein, resulting in lower mitochondrial complex IV activity and reduced the oxidative phosphorylation capacity of HEK cells [ 24 ]. In a similar manner, hindlimb immobilization increases metallothionein mRNA and produces a threefold decrease transcripts for enzymes involved in energy metabolism [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running

et al. 2015

View full text Add to dashboard Cite

In maturing rats, the growth of abdominal fat is attenuated by voluntary wheel running. After the cessation of running by wheel locking, a rapid increase in adipose tissue growth to a size that is similar to rats that have never run (i.e. catch-up growth) has been previously reported by our lab. In contrast, diet-induced increases in adiposity have a slower onset with relatively delayed transcriptomic responses. The purpose of the present study was to identify molecular pathways associated with the rapid increase in adipose tissue after ending 6 wks of voluntary running at the time of puberty. Age-matched, male Wistar rats were given access to running wheels from 4 to 10 weeks of age. From the 10th to 11th week of age, one group of rats had continued wheel access, while the other group had one week of wheel locking. Perirenal adipose tissue was extracted, RNA sequencing was performed, and bioinformatics analyses were executed using Ingenuity Pathway Analysis (IPA). IPA was chosen to assist in the understanding of complex ‘omics data by integrating data into networks and pathways. Wheel locked rats gained significantly more fat mass and significantly increased body fat percentage between weeks 10–11 despite having decreased food intake, as compared to rats with continued wheel access. IPA identified 646 known transcripts differentially expressed (p < 0.05) between continued wheel access and wheel locking. In wheel locked rats, IPA revealed enrichment of transcripts for the following functions: extracellular matrix, macrophage infiltration, immunity, and pro-inflammatory. These findings suggest that increases in visceral adipose tissue that accompanies the cessation of pubertal physical activity are associated with the alteration of multiple pathways, some of which may potentiate the development of pubertal obesity and obesity-associated systemic low-grade inflammation that occurs later in life.

show abstract

Section: Discussionmentioning

confidence: 99%

Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running

et al. 2015

View full text Add to dashboard Cite

show abstract

“…MT2A exerts antioxidant effects against mitochondrial superoxide [ 60 ]. Over expression of MT2A can decrease oxygen consumption, down-regulate cellular ATP levels and decrease oxidative phosphorylation capacity, and interact with mitochondrial complexes indirectly, which might be involved in the inhibition of certain respiratory enzymes via metal binding [ 61 ]. MT2A could suppress ischemia/reperfusion (I/R)-induced myocardial apoptosis mediated by mitochondrial stress [ 62 ] ( Figure 2 ).…”

Section: Mt2a and Oxidative Stressmentioning

confidence: 99%

Mammalian Metallothionein-2A and Oxidative Stress

Ling

Wei

Wang

et al. 2016

IJMS

View full text Add to dashboard Cite

Mammalian metallothionein-2A (MT2A) has received considerable attention in recent years due to its crucial pathophysiological role in anti-oxidant, anti-apoptosis, detoxification and anti-inflammation. For many years, most studies evaluating the effects of MT2A have focused on reactive oxygen species (ROS), as second messengers that lead to oxidative stress injury of cells and tissues. Recent studies have highlighted that oxidative stress could activate mitogen-activated protein kinases (MAPKs), and MT2A, as a mediator of MAPKs, to regulate the pathogenesis of various diseases. However, the molecule mechanism of MT2A remains elusive. A deeper understanding of the functional, biochemical and molecular characteristics of MT2A would be identified, in order to bring new opportunities for oxidative stress therapy.

show abstract

“…The expression of metallothionein proteins are suggested to become elevated in response to increased amounts of metals or reactive oxygen species (ROS) in the cell (for review see 28 ). On the other hand, when MT2A is overexpressed in HEK cells, the cells display reduced capacity for oxidative phosphorylation, thereby affecting their mitochondrial function 29 . These findings suggest that alterations in mitochondrial function may occur in cultured AD OM cells in a similar manner as observed in other cells in AD (reviewed in 30,31 ).…”

Section: Discussionmentioning

confidence: 99%

Disease specific alterations in the olfactory mucosa of patients with Alzheimer’s disease

Lampinen

Fazaludeen

Avesani

et al. 2020

Preprint

View full text Add to dashboard Cite

Olfactory dysfunction manifests in early stages of neurodegeneration in several disorders of the central nervous system. The sense of smell is orchestrated by the cells of the olfactory mucosa located in the upper nasal cavity, however, it is unclear how this tissue reflects key neurodegenerative features in Alzheimer’s disease (AD). Here we report that olfactory mucosa (OM) cells of patients with AD secrete increased amounts of toxic amyloid-beta. We detail cell-type specific gene expression patterns, unveiling 154 differentially expressed AD-associated genes compared to the cognitively normal controls, and 5 distinct cell populations in the cultures, together with disease-associated subpopulations. Overall, coordinated alteration of RNA and protein metabolism, inflammatory processes and signal transduction were observed in multiple cell types, suggesting a key role in AD pathophysiology. Our results demonstrate the potential of OM cultures as a new cellular model for AD. Moreover, for the first time we provide single cell transcript data for investigating the molecular and cellular mechanisms of AD in the OM.

show abstract

Metallothionein 2A affects the cell respiration by suppressing the expression of mitochondrial protein cytochrome c oxidase subunit II

Cited by 14 publications

References 42 publications

Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running

Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running

Mammalian Metallothionein-2A and Oxidative Stress

Disease specific alterations in the olfactory mucosa of patients with Alzheimer’s disease

Contact Info

Product

Resources

About