scholarly journals Age-Associated Changes in Ca2+-ATPase and Oxidative Damage in Sarcoplasmic Reticulum of Rat Heart

2012 ◽  
pp. 453-460 ◽  
Author(s):  
E. BABUŠÍKOVÁ ◽  
J. LEHOTSKÝ ◽  
D. DOBROTA ◽  
P. RAČAY ◽  
P. KAPLÁN

Altered Ca2+ handling may be responsible for the development of cardiac contractile dysfunctions with advanced age. In the present study, we investigated the roles of oxidative damage to sarcoplasmic reticulum (SR) and expression of Ca2+-ATPase (SERCA 2a) and phospholamban in age-associated dysfunction of cardiac SR. SR vesicles were prepared from hearts of 2-, 6-, 15-, and 26-month-old Wistar rats. Although activity of Ca2+-ATPase decreased with advancing age, no differences in relative amounts of SERCA 2a and phospholamban protein were observed. On the other hand, significant accumulation of protein oxidative damage occurred with aging. The results of this study suggest that age-related alteration in Ca2+-ATPase activity in the rat heart is not a consequence of decreased protein levels of SERCA 2a and phospholamban, but could arise from oxidative modifications of SR proteins. Cellular oxidative damage caused by reactive oxygen species could contribute to age-related alternations in myocardial relaxation.

2008 ◽  
pp. S49-S54
Author(s):  
E Babušíková ◽  
M Jeseňák ◽  
D Dobrota ◽  
N Tribulová ◽  
P Kaplán

The oxidative stress hypothesis of aging suggests that accumulation of oxidative damage is a key factor of the alterations in physiological function during aging. We studied age-related sensitivity to oxidative modifications of proteins and lipids of cardiac sarcoplasmic reticulum (SR) isolated from 6-, 15- and 26-month-old rats. Oxidative stress was generated in vitro by exposing SR vesicles to 0.1 mmol/l FeSO4/EDTA + 1 mmol/l H2O2 at 37 degrees C for 60 min. In all groups, oxidative stress was associated with decreased membrane surface hydrophobicity, as detected by 1-anilino-8-naphthalenesulfonate as a probe. Structural changes in SR membranes were accompanied by degradation of tryptophan and significant accumulation of protein dityrosines, protein conjugates with lipid peroxidation products, conjugated dienes and thiobarbituric acid reactive substances. The sensitivity to oxidative damage was most pronounced in SR of 26-month-old rat. Our results indicate that aging and oxidative stress are associated with accumulation of oxidatively damaged proteins and lipids and these changes could contribute to cardiovascular injury.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Xia Wang ◽  
Yan-jun Cui ◽  
Jia Qi ◽  
Min-min Zhu ◽  
Tian-liang Zhang ◽  
...  

Several previous studies have demonstrated the excellent antioxidant activity of fucoxanthin against oxidative stress which is closely related to the pathogenesis of liver diseases. The present work was to investigate whether fucoxanthin could protect human hepatic L02 cells against hydrogen peroxide- (H2O2-) induced oxidative damage. Its effects on H2O2-induced cell viability, lactate dehydrogenase (LDH) leakage, intracellular reduced glutathione, and reactive oxygen species (ROS) contents, along with mRNA and protein relative levels of the cytoprotective genes including Nrf2, HO-1, and NQO1, were investigated. The results showed that fucoxanthin could upregulate the mRNA and protein levels of the cytoprotective genes and promote the nuclear translocation of Nrf2, which could be inhibited by the PI3K inhibitor of LY294002. Pretreatment of fucoxanthin resulted in decreased LDH leakage and intracellular ROS content but enhanced intracellular reduced glutathione. Interestingly, pretreatment using fucoxanthin protected against the oxidative damage in a nonconcentration-dependent manner, with fucoxanthin of 5 μM demonstrating the optimal effects. The results suggest that fucoxanthin exerts cytoprotective effects against H2O2-induced oxidative damage in L02 cells, which may be through the PI3K-dependent activation of Nrf2 signaling.


2005 ◽  
Vol 288 (3) ◽  
pp. E526-E533 ◽  
Author(s):  
Jonathan D. Schertzer ◽  
David R. Plant ◽  
James G. Ryall ◽  
Felice Beitzel ◽  
Nicole Stupka ◽  
...  

Aging is associated with a slowing of skeletal muscle contractile properties, including a decreased rate of relaxation. In rats, the age-related decrease in the maximal rate of relaxation is reversed after 4-wk administration with the β2-adrenoceptor agonist (β2-agonist) fenoterol. Given the critical role of the sarcoplasmic reticulum (SR) in regulating intracellular Ca2+ transients and ultimately the time course of muscle contraction and relaxation, we tested the hypothesis that the mechanisms of action of fenoterol are mediated by alterations in SR proteins. Sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) kinetic properties were assessed in muscle homogenates and enriched SR membranes isolated from the red (RG) and white (WG) portions of the gastrocnemius muscle in adult (16 mo) and aged (28 mo) F344 rats that had been administered fenoterol for 4 wk (1.4 mg/kg/day ip, in saline) or vehicle only. Aging was associated with a 29% decrease in the maximal activity ( Vmax) of SERCA in the RG but not in the WG muscles. Fenoterol treatment increased the Vmax of SERCA and SERCA1 protein levels in RG and WG. In the RG, fenoterol administration reversed an age-related selective nitration of the SERCA2a isoform. Our findings demonstrate that the mechanisms underlying age-related changes in contractile properties are fiber type dependent, whereas the effects of fenoterol administration are independent of age and fiber type.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261087
Author(s):  
Maximiliano J. Vallejos ◽  
Abdunaser Eadaim ◽  
Eu-Teum Hahm ◽  
Susan Tsunoda

Age-related changes in ion channel expression are likely to affect neuronal signaling. Here, we examine how age affects Kv4/Shal and Kv1/Shaker K+ channel protein levels in Drosophila. We show that Kv4/Shal protein levels decline sharply from 3 days to 10 days, then more gradually from 10 to 40 days after eclosion. In contrast, Kv1/Shaker protein exhibits a transient increase at 10 days that then stabilizes and eventually declines at 40 days. We present data that begin to show a relationship between reactive oxygen species (ROS), Kv4/Shal, and locomotor performance. We show that Kv4/Shal levels are negatively affected by ROS, and that over-expression of Catalase or RNAi knock-down of the ROS-generating enzyme, Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase (NOX), can attenuate the loss of Kv4/Shal protein. Finally, we compare levels of Kv4.2 and Kv4.3 in the hippocampus, olfactory bulb, cerebellum, and motor cortex of mice aged 6 weeks and 1 year. While there was no global decline in Kv4.2/4.3 that parallels what we report in Drosophila, we did find that Kv4.2/4.3 are differentially affected in various brain regions; this survey of changes may help inform mammalian studies that examine neuronal function with age.


2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
B. Poljsak ◽  
I. Milisav ◽  
T. Lampe ◽  
I. Ostan

High levels of reactive oxygen species (ROS) compared to antioxidant defenses are considered to play a major role in diverse chronic age-related diseases and aging. Here we present an attempt to synthesize information about proximate oxidative processes in aging (relevant to free radical or oxidative damage hypotheses of aging) with an evolutionary scenario (credited here to Dawkins hypotheses) involving tradeoffs between the costs and benefits of oxidative stress to reproducing organisms. Oxidative stress may be considered a biological imperfection; therefore, the Dawkins' theory of imperfect adaptation of beings to environment was applied to the role of oxidative stress in processes like famine and infectious diseases and their consequences at the molecular level such as mutations and cell signaling. Arguments are presented that oxidative damage is not necessarily an evolutionary mistake but may be beneficial for reproduction; this may prevail over its harmfulness to health and longevity in evolution. Thus, Dawkins' principle of biological “malevolence” may be an additional biological paradigm for explaining the consequences of oxidative stress.


2014 ◽  
Vol 61 (4) ◽  
Author(s):  
Ana Šarić ◽  
Sandra Sobočanec ◽  
Željka Mačak Šafranko ◽  
Marijana Popović-Hadžija ◽  
Gorana Aralica ◽  
...  

Increased oxygen concentration (hyperoxia) induces oxidative damage of tissues and organs. Oxygen toxicity in hyperoxia is controlled by factors such as sex, age, tissue, strain and hormones. In most species females show lower incidence of some age-related pathologies linked with oxidative stress, which has been attributed to a beneficial effect of ovarian hormones. In this study we found that hyperoxia induced hepatic oxidative damage exclusively in male CBA/H mice, followed by their decreased survival. Histopathological examination revealed that the observed differences in survival were not the consequence of acute lung injury induced by hyperoxia. Next, we observed that an increased Sirt1 protein level in hyperoxia-exposed female CBA/H mice correlated with their lower PPAR-γ and higher eNOS and Sod2 protein levels. In males, higher PPAR-γ and lower Sod2 protein levels were associated with unchanged Sirt1 expression. Although these results are of a correlative nature only, they clearly show that females show better survival, increased resistance to hyperoxia and have generally more efficient defense systems, which suggests that their headstart in resistance to hyperoxia could be a consequence of the beneficial effect of ovarian hormones.


1985 ◽  
Vol 86 (5) ◽  
pp. 637-651 ◽  
Author(s):  
C H Orchard ◽  
E G Lakatta

The purposes of the present study were to determine (a) whether changes of intracellular [Ca2+] (Cai) can account for the decrease of developed tension observed in rat heart muscle when stimulation rate is increased, and (b) whether the effect of stimulation rate on Cai is altered in conditions in which the rate of repriming of the sarcoplasmic reticulum (SR) is altered, as when perfusate [Ca2+] (Cao) is increased, and in heart muscle from senescent animals. The photoprotein aequorin was used to monitor Cai in rat papillary muscles. In muscles from 6-mo-old rats, increasing the stimulation rate in the range 0.2-0.66 Hz led to parallel decreases of both the aequorin light transient and developed tension when Cao was 2 mM. When Cao was increased to 4 mM, changes in the stimulation rate had less effect on both the light transient and tension. At 8 mM Cao, changing the stimulation rate had no effect on either the light transient or developed tension. Papillary muscles from 24-mo-old rats, in which SR function is likely to be depressed, exhibited a prolonged Ca2+ transient and twitch. At a Cao of 4 or 8 mM, increasing the stimulation rate from 0.33 to 0.66 Hz still led to decreases in the size of the aequorin light transient and developed tension in these muscles. Developed tension and aequorin light responded to increases of Cao in the same way in both groups of muscles. We conclude that under the conditions of our experiments, developed tension is determined by Cai. The negative interval-strength relationship observed when Cao is in the physiological range can be accounted for by a time-dependent recycling of Ca2+ by the SR. The effects of increasing Cao and the age-related differences observed at high Cao can also be accounted for using this model.


2017 ◽  
Vol 334 ◽  
pp. 78-85 ◽  
Author(s):  
Cláudia Vanzella ◽  
Juliana Dalibor Neves ◽  
Adriana Fernanda Vizuete ◽  
Dirceu Aristimunha ◽  
Janaína Kolling ◽  
...  

2020 ◽  
Vol 21 (4) ◽  
pp. 53-59
Author(s):  
A.D. Chuprov ◽  
◽  
V.M. Treushnikov ◽  
S.V. Notova ◽  
S.M. Kim ◽  
...  

The elemental composition of cataract and non-cataract crystalline lenses was studied in this study. The study was carried out on Wistar rats (n = 30), two groups were formed: control and experimental. The animals of the experimental group were simulated age-related cataract using ultraviolet irradiation for 6 months. The sample collection of lenses was carried out after 2 (the early stages of cataract) and 6 months (the mature stages of cataract) of the experiment. The chemical composition of the samples was determined using by ICP-AES and ICP-MS. The generation of reactive oxygen species under the action of ultraviolet radiation leads to a change in the permeability of cell membranes and, as a consequence, to a disturbance of homeostasis of elements. There is an imbalance of macronutrients in the lenses with the progress of cataract accompanying by an increase in the level of calcium and sodium and decrease in potassium, magnesium and phosphorus.


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