Paraoxical relationship between protein content and nucleolar activity in mammalian cardiomyocytes

Genome ◽  
2004 ◽  
Vol 47 (3) ◽  
pp. 565-578 ◽  
Author(s):  
Olga V Anatskaya ◽  
Alexander E Vinogradov

It was recently demonstrated that polyploidization of the avian myocardium is associated with a reduction of cardiac aerobic capacity evaluated by the heart mass to body mass ratio (heart index). To investigate possible cellular correlates of polyploidization, the protein content and nucleolar activity per cell and per genome were examined by image cytometry in 21 mammalian species, differing in the degree of heart polyploidization and heart index. We found that average cardiomyocyte ploidy level correlates negatively with the animal heart index (r = –0.75, p < 10–4), i.e., the large heart of athletic mammals is polyploidized to a lesser degree than the relatively smaller heart of sedentary species, which confirms the picture observed in birds. The protein content per genome decreased with the elevation of cardiomyocyte ploidy level. This inverse correlation was especially pronounced with the removed effect of body mass (r = –0.79, p < 10–4). Surprisingly, these changes were accompanied by the increase of nucleolar activity per genome (r = 0.61, p < 10–3). In the two species, for which the microarray gene expression data were available (human and mouse), this increase was paralleled by the elevated expression of ribosomal protein genes (but there was no increase in the expression of tissue-specific genes). Thus, in the polyploid cardiomyocytes there is a misbalance between protein content per genome and ribosome biogenesis. The reduction of protein content (per genome) of polyploid cardio my ocytes should further curtail heart functionality (in addition to reduction of heart index), because it is known that cardio myocyte protein content consists of more than 90% contractile proteins. This finding makes doubtful a widespread notion that polyploidization is necessary for cell function. Because somatic polyploidization is associated with stressful conditions and impaired energetics, we suppose that additional genomes can serve for cell regeneration and as a defense against oxidative damage in the organs that work at the limit of their metabolic capacity.Key words: somatic polyploidy, heart, functional capacity, protein–DNA ratio.

Pancreas ◽  
2017 ◽  
Vol 46 (3) ◽  
pp. 358-365 ◽  
Author(s):  
Johan Staaf ◽  
Viktor Labmayr ◽  
Katharina Paulmichl ◽  
Hannes Manell ◽  
Jing Cen ◽  
...  

2013 ◽  
Vol 24 (2) ◽  
pp. 115-128 ◽  
Author(s):  
Aaron Z. Welch ◽  
Patrick A. Gibney ◽  
David Botstein ◽  
Douglas E. Koshland

Tolerance to desiccation in cultures of Saccharomyces cerevisiae is inducible; only one in a million cells from an exponential culture survive desiccation compared with one in five cells in stationary phase. Here we exploit the desiccation sensitivity of exponentially dividing cells to understand the stresses imposed by desiccation and their stress response pathways. We found that induction of desiccation tolerance is cell autonomous and that there is an inverse correlation between desiccation tolerance and growth rate in glucose-, ammonia-, or phosphate-limited continuous cultures. A transient heat shock induces a 5000–fold increase in desiccation tolerance, whereas hyper-ionic, -reductive, -oxidative, or -osmotic stress induced much less. Furthermore, we provide evidence that the Sch9p-regulated branch of the TOR and Ras-cAMP pathway inhibits desiccation tolerance by inhibiting the stress response transcription factors Gis1p, Msn2p, and Msn4p and by activating Sfp1p, a ribosome biogenesis transcription factor. Among 41 mutants defective in ribosome biogenesis, a subset defective in 60S showed a dramatic increase in desiccation tolerance independent of growth rate. We suggest that reduction of a specific intermediate in 60S biogenesis, resulting from conditions such as heat shock and nutrient deprivation, increases desiccation tolerance.


Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1124 ◽  
Author(s):  
Sergio Verd ◽  
Gemma Ginovart ◽  
Javier Calvo ◽  
Jaume Ponce-Taylor ◽  
Antoni Gaya

The aim of this review is to evaluate changes in protein parameters in the second year postpartum. There is considerable agreement among authors about the declining trend of human milk protein concentrations, but most research on protein content in breast milk focuses on the first year of life and comes from developed countries. Whereas this is the case for exclusive breastfeeding or for breastfeeding into the first year of life, the opposite applies to weaning or extended breastfeeding. This review is predominantly based on observational epidemiological evidence and on comparative research linking breast milk composition with cutting down on breastfeeding. Studies dating back several decades have shown an increase in the proportion of immunoglobulins, lactoferrin, and serum albumin during weaning. According to the limited data available, it seems likely that the regulation of milk protein composition during involution can be ascribed to alterations in tight junctions. In studies on humans and other mammalian species, offspring suckle more from mothers that produce more dilute milk and the increase in milk protein concentration is positively correlated to a decrease in suckling frequency during weaning. High milk protein contents were first reported in nonindustrial communities where breastfeeding is sustained the longest, but recent papers from urbanized communities have taken credit for rediscovering the increase in protein content of human milk that becomes evident with prolonged breastfeeding. This review presents an overview of the changes in breast milk protein parameters in the second year postpartum to enable milk banks’ practitioners to make informed nutritional decisions on preterm infants.


Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2031
Author(s):  
Neda S. Akhavan ◽  
Shirin Pourafshar ◽  
Sarah A. Johnson ◽  
Elizabeth M. Foley ◽  
Kelli S. George ◽  
...  

Type 2 diabetes (T2D) is a major contributor to morbidity and mortality largely due to increased cardiovascular disease risk. This study examined the relationships among protein consumption and sources on glycemic control and cardiovascular health in individuals with prediabetes and T2D. Sixty-two overweight or obese participants with prediabetes or T2D, aged 45–75 years were stratified into the following three groups based on protein intake: <0.8 g (gram)/kg (kilogram) body weight (bw), ≥0.8 but <1.0 g/kg bw, and ≥1.0 g/kg bw as below, meeting, and above the recommended levels of protein intake, respectively. Body mass, body mass index (BMI), hip circumference (HC), waist circumference (WC), lean mass, and fat mass (FM) were significantly higher in participants who consumed below the recommended level of protein intake as compared with other groups. Higher animal protein intake was associated with greater insulin secretion and lower triglycerides (TG). Total, low-density, and high-density cholesterol were significantly higher in participants who met the recommended protein intake as compared with the other groups. These data suggest that high protein consumption is associated with lower BMI, HC, WC, and FM, and can improve insulin resistance without affecting lipid profiles in this population. Furthermore, higher intake of animal protein can improve β-cell function and lower plasma TG.


Endocrinology ◽  
2016 ◽  
Vol 157 (11) ◽  
pp. 4234-4245 ◽  
Author(s):  
Charles E. Roselli ◽  
Rebecka Amodei ◽  
Kyle P. Gribbin ◽  
Keely Corder ◽  
Fred Stormshak ◽  
...  

Prenatal exposure to excess androgen may result in impaired adult fertility in a variety of mammalian species. However, little is known about what feedback mechanisms regulate gonadotropin secretion during early gestation and how they respond to excess T exposure. The objective of this study was to determine the effect of exogenous exposure to T on key genes that regulate gonadotropin and GnRH secretion in fetal male lambs as compared with female cohorts. We found that biweekly maternal testosterone propionate (100 mg) treatment administered from day 30 to day 58 of gestation acutely decreased (P &lt; .05) serum LH concentrations and reduced the expression of gonadotropin subunit mRNA in both sexes and the levels of GnRH receptor mRNA in males. These results are consistent with enhanced negative feedback at the level of the pituitary and were accompanied by reduced mRNA levels for testicular steroidogenic enzymes, suggesting that Leydig cell function was also suppressed. The expression of kisspeptin 1 mRNA, a key regulator of GnRH neurons, was significantly greater (P &lt; .01) in control females than in males and reduced (P &lt; .001) in females by T exposure, indicating that hypothalamic regulation of gonadotropin secretion was also affected by androgen exposure. Although endocrine homeostasis was reestablished 2 weeks after maternal testosterone propionate treatment ceased, additional differences in the gene expression of GnRH, estrogen receptor-β, and kisspeptin receptor (G protein coupled receptor 54) emerged between the treatment cohorts. These changes suggest the normal trajectory of hypothalamic-pituitary axis development was disrupted, which may, in turn, contribute to negative effects on fertility later in life.


Author(s):  
Raquel Barba ◽  
Josep Bisbe ◽  
José Nicolas Alcalá Pedrajas ◽  
Jesús Toril ◽  
Rafael Monte ◽  
...  

Background The relationship between body mass index (BMI) and mortality in patients with established arterial disease remains controversial. Methods FRENA is an ongoing, observational registry of consecutive outpatients with coronary artery disease (CAD), cerebrovascular disease, or peripheral artery disease (PAD). We examined the prognostic importance of accepted BMI categories on outcome among patients in the FRENA registry. Results In April 2008, 2274 patients (mean age, 66 years) had been enrolled, of whom 14 (0.6%) were underweight; 533 (23%) normal; 1051 (46%) overweight; and 676 (30%) were obese. Over a mean follow-up of 14 months, the incidence of major cardiovascular events (myocardial infarction, ischemic stroke, or critical limb ischemia) per 100 patient-years was: 7.1 [95% confidence interval (CI): 0.4–35]; 11 (95% CI: 8.4–14); 6.9 (95% CI: 5.6–8.5); and 8.5 (95% CI: 6.6–11), respectively. Their cardiovascular mortality was: 7.1 (95% CI: 0.4–35); 4.1 (95% CI: 5.9–11); 1.3 (95% CI: 0.9–2.3); and 1.5 (95% CI: 1.4–3.5), respectively. On multivariate analysis, the hazard ratio for cardiovascular mortality was: 2.2 (95% CI: 0.3–17); 1.0 (reference); 0.37 (95% CI: 0.20–0.69); and 0.37 (95% CI: 0.18–0.73), respectively. Survival benefit was only found in patients with CAD or PAD. Weight loss had little influence on outcome. Conclusion Patients with CAD or PAD (not those with cerebrovascular disease) have an inverse correlation between BMI and cardiovascular mortality, even after adjusting for confounding variables.


Medicina ◽  
2006 ◽  
Vol 43 (1) ◽  
pp. 10 ◽  
Author(s):  
Gražina Drąsutienė ◽  
Janina Tutkuvienė ◽  
Jolita Zakarevičienė ◽  
Diana Ramašauskaitė ◽  
Žaneta Kasilovskienė ◽  
...  

Objective. To evaluate changes in anthropometric and biochemical parameters in pregnancy and their dynamics during last two decades and to determine the association between anthropometric and biochemical parameters, their influence on fetal and neonatal development. Material and methods. In 1985–2005, anthropometric (height, body mass, weight gain during pregnancy, pelvic measurements, skinfold thicknesses, passive body mass) and biochemical (cholesterol, triglyceride, protein, and iron levels) parameters, their correlation, changes in pregnancy were examined; also the correlations between these parameters and neonatal body mass indices were evaluated. In 1986–1987, 383 pregnant women were examined, in 1998 – 130, and in 2003–2005 – 133. Results. During 20 years, the height of examined women increased on an average of 2.5 cm; they became thinner; body mass index decreased. The body composition became similar to “cylinder” shape due to decreased thickness of adipose tissue in the limbs. The dimensions of bony pelvis – external conjugate and bicristal diameters – decreased. Primiparous women became older (1995 – 22.5 years of age, 2004 – 27.6). At the beginning of investigation, the weight gain was on an average of 21.9% of body mass before pregnancy (13.3 kg) and at the end – 23.9% (14.2 kg). The values of anthropometric parameters vary in a consistent pattern during pregnancy: the lower body mass and body mass index at the beginning of pregnancy, the higher weight gain at the end of pregnancy. Blood serum levels of cholesterol, triglycerides, and especially iron were decreased during the study. Conclusions. An inverse correlation between body mass index and lipid metabolism in pregnancy was revealed: the higher body mass index was at the beginning of pregnancy, the lower increase in lipid concentration was during pregnancy. At the beginning of investigation as well as after 20 years, women with low body mass index showed the most significant anthropometric and lipid metabolic changes in pregnancy.


2008 ◽  
Vol 74 (6) ◽  
pp. 469-475 ◽  
Author(s):  
Ronald H. Clements ◽  
Kishore Yellumahanthi ◽  
Mary Wesley ◽  
Naveen Ballem ◽  
Kirby I. Bland

Hyperparathyroidism (HPT) can occur after gastric bypass because of the alteration in vitamin D and calcium absorption. Adequate serum vitamin D concentrations have not been clearly defined in this patient population. Vitamin D (Vit D) and parathyroid hormone (PTH) were assessed 1 year after laparoscopic gastric bypass (LGB). The prevalence of HPT and Vit D deficiency were determined and their association was evaluated using Fisher's exact test. Ninety-three patients (aged 44 ± 1.1 years, 49.6 ± 0.67 kg/m2 body mass index, 79.6% female, 69.6% white) were evaluated. The prevalence of Vit D deficiency (less than 20 ng/mL) and HPT (greater than 65 pg/mL) was 23.6 per cent (n = 22) and 25.7 per cent (n = 28), respectively. Among patients with HPT, only eight of 28 (28.6%) had Vit D deficiency, and of those with Vit D deficiency, only eight of 22 (36.4%) had HPT. There was a weak inverse correlation (r = –0.37) between PTH and Vit D. Blacks are at higher risk for Vit D deficiency. There was no significant association between Vit D deficiency and HPT, Vit D deficiency and Roux limb length, or HPT and Roux limb length. After LGB, Vit D deficiency and hyperparathyroidism occur commonly. Body mass index and Roux limb length are not associated with these two conditions, but racial differences do exist. There is a weak inverse correlation between Vit D and PTH. Further research is needed to elucidate the causes, treatments, and significance of HPT after LGB.


2020 ◽  
Vol 21 (4) ◽  
pp. 1230
Author(s):  
Gangqiao Kuang ◽  
Wenjing Tao ◽  
Shuqing Zheng ◽  
Xiaoshuang Wang ◽  
Deshou Wang

Ribosomal proteins (RPs) are indispensable in ribosome biogenesis and protein synthesis, and play a crucial role in diverse developmental processes. In the present study, we carried out a comprehensive analysis of RPs in chordates and examined the expression profiles of the complete set of 92 cytoplasmic RP genes in Nile tilapia. The RP genes were randomly distributed throughout the tilapia genome. Phylogenetic and syntenic analyses revealed the existence of duplicated RP genes from 2R (RPL3, RPL7, RPL22 and RPS27) and 3R (RPL5, RPL19, RPL22, RPL41, RPLP2, RPS17, RPS19 and RPS27) in tilapia and even more from 4R in common carp and Atlantic salmon. The RP genes were found to be expressed in all tissues examined, but their expression levels differed among different tissues. Gonadal transcriptome analysis revealed that almost all RP genes were highly expressed, and their expression levels were highly variable between ovaries and testes at different developmental stages in tilapia. No sex- and stage-specific RP genes were found. Eleven RP genes displayed sexually dimorphic expression with nine higher in XY gonad and two higher in XX gonad at all stages examined, which were proved to be phenotypic sex dependent. Quantitative real-time PCR and immunohistochemistry ofRPL5b and RPL24 were performed to validate the transcriptome data. The genomic resources and expression data obtained in this study will contribute to a better understanding of RPs evolution and functions in chordates.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4554-4554
Author(s):  
Despoina Adamidou ◽  
Erasmia Rouka ◽  
Evgenia Verrou ◽  
Giannis Koutsaliaris ◽  
Anna Lazaridou ◽  
...  

Abstract Background: the metalloprotease ADAMTS13 ( A Disintegrin And Metalloprotease with ThromboSpondin type 1 motif 13) cleaves von Willebrand within nascent platelet rich thrombi and its functional deficiency is associated with acute idiopathic or congenital thrombotic thrombocytopenic purpura (TTP). This disorder occurs more frequently in women especially during late pregnancy and postpartum period. However there is little information, some times controversial, on the protease behavior among healthy individuals in terms of gender and other demographic factors. Materials and methods: samples from 92 healthy Greek blood donors of childbearing age (17–50) were submitted. Fifty males, 42 females were tested (median age 38/33 respectively). The ADAMTS13 activity was measured by fluorescent technique (FRETS normal range &gt;65%). Von Willebrand Factor Antigen and Activity as well as FVIII Activity were estimated by automated latex enhanced immunoassay. Whole blood count was determined concurrently. ABO phenotyping was performed. Demographic data (body mass index, blood pressure, parity) and social habits (cigarette smoking, alcohol intake ) were recorded. Pregnancy, preaclampsia, personal or family history of miscarriage, bleeding/thromboembolism, hypertension, use of oral contraception pills or any other medication were defined as exclusion criteria. All data were analyzed by Mann Whitney U-test, Kruskal Wallis statistics and Spearman’s correlations. All individuals signed informed consent before sampling. Aim: we conducted a prospective study in order to measure ADAMTS13 activity in healthy population and identify possible factors that may influence enzyme’s range. Results: statistical significance was obtained when we examined ADAMTS13 activity in terms of gender (138,42% versus 109,12 %-mean values-for males and females respectively, p&lt;0,001). We found protease’s activity below normal in 5 cases ( 4 females 26% –55%, 1 male 45% ) without any clinical relevance. Overall, there was a strong positive correlation between VWF:Ag and FVIII activity (p&lt;0.001) and between VWF:Ag and VWF:Activity (p&lt;0,001). Although ADAMTS13 activity decreased slightly with VWF:Ag increase there was no statistically significant inverse correlation between them. There was no difference in ADAMTS13 activity for the different blood groups. Negative correlation was revealed between platelets count and enzyme’s activity (p=0.005). In females, nulliparous group reached lower values of ADAMTS13 activity compared to those of parous women though without statistical significance. There were no correlations between ADAMTS13 activity and age, body mass index or cigarette and alcohol use. Conclusions: the main finding of the present study is that plasma levels of ADAMTS13 activity differed significantly between the two genders. Yet previous studies have shown controversial results. In our knowledge this is the first attempt to measure ADAMTS13 activity in Greeks healthy individuals with age restriction (childbearing adults). In agreement with current literature on ADAMTS13 activity in pregnancy, where there is progressive decrease during gestation, we speculate the feasibility of oestrogen control over protease levels. Our results indicate probable hormonal penetration as mechanism which in part explains the different values we found between men and women. Probably is the lower ADAMTS13 activity, yet within normal, compared to men’s, that leaves women more prone to TTP under predisposing conditions. This together with the preference of autoimmunity for women may offer an explanation on the higher incidence of TTP in females. The inverse correlation between ADAMTS13 activity and platelets count was unexpected and needs to be further investigated.


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