Phosphorylation of αB-crystallin in the myocardium: Analysis of relations with aging and cardiomyopathy

Muraleva, Natalia A.; Devyatkin, V. A.; Kolosova, N. G.

doi:10.1016/j.exger.2017.05.009

Cited by 11 publications

(10 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tetsuo Y et al’s study demonstrates that the levels of αB-crystallin phosphorylation at S59 and, to some extent, at S45 are increased in aged muscles. Phosphorylated αB-crystallin affects functional and structural properties of cardiomyocytes that are crucial for contractile function and myofibrillar organization [ 20 ]. By building phosphomimetic knock-in mouse models, Aryal N et al proved that constitutive Dicer1 phosphorylation accelerates metabolism and aging in vivo [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Increased cytochrome C threonine 50 phosphorylation in aging heart as a novel defensive signaling against hypoxia/reoxygenation induced apoptosis

Sun

Lin

et al. 2022

Aging

View full text Add to dashboard Cite

Previous studies have shown that aging promotes myocardial apoptosis. However, the detailed mechanisms remain unclear. Our recent studies revealed that aging not only activates apoptosis, but also activates some antiapoptotic factors. By quantitative phosphoproteomics, here we demonstrated that aging increases cytochrome c (Cytc) phosphorylation at threonine 50 (T50), a post-translational modification with unknown functional impact. With point mutation and lentivirus transfection, cardiomyocytes were divided into four groups: empty vector group, WT (wild type), T50E (as a phosphomimic variant), and T50A (non-phosphorylatable). TUNEL staining and flow cytometry were used to determine the apoptosis ratio in different groups after hypoxic/reoxygenated (H/R) treatment. The results showed that T50-phosphorylated Cytc suppressed myocardial apoptosis induced by H/R. Furthermore, Western Blot and ELISA measurements revealed that Cytc T50 phosphorylation inhibited caspase-9 and caspase-3 activity without altering caspase-8, BCL-2, BCL-XL, and Bax expression. In our study, we demonstrated that aging increases phosphorylation Cytc at T50 and this aging-increasing phosphorylation site can suppress H/R-induced apoptosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased cytochrome C threonine 50 phosphorylation in aging heart as a novel defensive signaling against hypoxia/reoxygenation induced apoptosis

Sun

Lin

et al. 2022

Aging

View full text Add to dashboard Cite

show abstract

“…It is known that hypertension can result in hypertrophic cardiomyopathy. Despite the differences in hypertension severity, both rat strains-ISIAH [37] and OXYS [38]-are known to develop hypertrophic cardiomyopathy. At the same time, in ISIAH rats, there are no other manifestations of accelerated senescence that are typical for OXYS rats, including signs of accelerated brain aging.…”

Section: Discussionmentioning

confidence: 99%

Single-Nucleotide Polymorphisms (SNPs) Both Associated with Hypertension and Contributing to Accelerated-Senescence Traits in OXYS Rats

Devyatkin

Redina

Muraleva

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Aging is a major risk factor of numerous human diseases. Adverse genetic variants may contribute to multiple manifestations of aging and increase the number of comorbid conditions. There is evidence of links between hypertension and age-related diseases, although the genetic relationships are insufficiently studied. Here, we investigated the contribution of hypertension to the development of accelerated-senescence syndrome in OXYS rats. We compared transcriptome sequences of the prefrontal cortex, hippocampus, and retina of OXYS rats with the genotypes of 45 rat strains and substrains (which include models with hypertension) to find single-nucleotide polymorphisms (SNPs) both associated with hypertension and possibly contributing to the development of age-related diseases. A total of 725 polymorphisms were common between OXYS rats and one or more hypertensive rat strains/substrains being analyzed. Multidimensional scaling detected significant similarities between OXYS and ISIAH rat genotypes and significant differences between these strains and the other hypertensive rat strains/substrains. Nonetheless, similar sets of SNPs produce a different phenotype in OXYS and ISIAH rats depending on hypertension severity. We identified 13 SNPs causing nonsynonymous amino-acid substitutions having a deleterious effect on the structure or function of the corresponding proteins and four SNPs leading to functionally significant structural rearrangements of transcripts in OXYS rats. Among them, SNPs in genes Ephx1, Pla2r1, and Ccdc28b were identified as candidates responsible for the concomitant manifestation of hypertension and signs of accelerated aging in OXYS rats.

show abstract

“…CryAB R120G -induced cardiomyopathy has been established to occur along with reductive stress-induced GSH/GSSG imbalance ( Figure 5) [11]. It is reported that during aging and during the progression of cardiomyopathy, both CryAB and its phosphorylation are elevated [118,119]. The molecular tweezer CLR01 protects against CryAB R120G -induced cytotoxicity, hampers CryAB R120G -induced protein aggregation, and alleviates proteotoxicity in cardiomyocytes [120].…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

Reductive Stress-Induced Mitochondrial Dysfunction and Cardiomyopathy

Tao

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

The goal of this review was to summarize reported studies focusing on cellular reductive stress-induced mitochondrial dysfunction, cardiomyopathy, dithiothreitol- (DTT-) induced reductive stress, and reductive stress-related free radical reactions published in the past five years. Reductive stress is considered to be a double-edged sword in terms of antioxidation and disease induction. As many underlying mechanisms are still unclear, further investigations are obviously warranted. Nonetheless, reductive stress is thought to be caused by elevated levels of cellular reducing power such as NADH, glutathione, and NADPH; and this area of research has attracted increasing attention lately. Albeit, we think there is a need to conduct further studies in identifying more indicators of the risk assessment and prevention of developing heart damage as well as exploring more targets for cardiomyopathy treatment. Hence, it is expected that further investigation of underlying mechanisms of reductive stress-induced mitochondrial dysfunction will provide novel insights into therapeutic approaches for ameliorating reductive stress-induced cardiomyopathy.

show abstract

Phosphorylation of αB-crystallin in the myocardium: Analysis of relations with aging and cardiomyopathy

Cited by 11 publications

References 27 publications

Increased cytochrome C threonine 50 phosphorylation in aging heart as a novel defensive signaling against hypoxia/reoxygenation induced apoptosis

Increased cytochrome C threonine 50 phosphorylation in aging heart as a novel defensive signaling against hypoxia/reoxygenation induced apoptosis

Single-Nucleotide Polymorphisms (SNPs) Both Associated with Hypertension and Contributing to Accelerated-Senescence Traits in OXYS Rats

Reductive Stress-Induced Mitochondrial Dysfunction and Cardiomyopathy

Contact Info

Product

Resources

About