Impact of Aging on Calcium Signaling and Membrane Potential in Endothelium of Resistance Arteries: A Role for Mitochondria

Behringer, Erik J.; Segal, Steven S.

doi:10.1093/gerona/glx079

Cited by 28 publications

(21 citation statements)

References 89 publications

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“…no. M22426, Molecular Probes, Eugene OR, USA) (Behringer & Segal, ) for 30 min at 37°C in combination with Hoechst 33342 dye (1 µ m ). For immunostaining, vessels were fixed in 2% paraformaldehyde for 1 h followed by a mild collagenase treatment (1.5 mg ml −1 ; Cat.…”

Section: Methodsmentioning

confidence: 99%

Advanced age protects resistance arteries of mouse skeletal muscle from oxidative stress through attenuating apoptosis induced by hydrogen peroxide

Norton

Sinkler

Jacobsen

et al. 2019

The Journal of Physiology

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Key pointsr Vascular oxidative stress increases with advancing age. r We hypothesized that resistance vessels develop resilience to oxidative stress to protect functional integrity and tested this hypothesis by exposing isolated pressurized superior epigastric arteries (SEAs) of old and young mice to H 2 O 2 . r H 2 O 2 -induced death was greater in smooth muscle cells (SMCs) than endothelial cells (ECs) and lower in SEAs from old vs. young mice; the rise in vessel wall [Ca 2+ ] i induced by H 2 O 2 was attenuated with ageing, as was the decline in noradrenergic vasoconstriction; genetic deletion of IL-10 mimicked the effects of advanced age on cell survival. r Inhibiting NO synthase or scavenging peroxynitrite reduced SMC death; endothelial denudation or inhibiting gap junctions increased SMC death; delocalization of cytochrome C activated caspases 9 and 3 to induce apoptosis.r Vascular cells develop resilience to H 2 O 2 during ageing by preventing Ca 2+ overload and endothelial integrity promotes SMC survival.Abstract Advanced age is associated with elevated oxidative stress and can protect the endothelium from cell death induced by H 2 O 2 . Whether such protection occurs for intact vessels or differs between smooth muscle cell (SMC) and endothelial cell (EC) layers is unknown. We tested the hypothesis that ageing protects SMCs and ECs during acute exposure to H 2 O 2 (200 µM, 50 min). Mouse superior epigastric arteries (SEAs; diameter, ß150 µm) were isolated and pressurized to 100 cmH 2 O at 37˚C. For SEAs from young (4 months) mice, H 2 O 2 killed 57% of SMCs and 11% of ECs in males vs. 8% and 2%, respectively, in females. Therefore, SEAs from males were studied to resolve the effect of ageing and experimental interventions. For old (24 months) Charles E. Norton III is currently a postdoctoral fellow in Steven Segal's laboratory at the University of Missouri, Columbia. His interest in vascular physiology developed as an undergraduate and PhD student studying mechanisms of chronic hypoxia-induced pulmonary hypertension at the University of New Mexico. Dr Norton's primary interest is in understanding how chemical and electrical communication between endothelial cells and smooth muscle cells modulate vasomotor tone and cell death. Currently, he is exploring how conditions of chronic oxidative stress alter resilience to apoptosis.C. E. Norton and others J Physiol 597.15 mice, SMC death was reduced to 10% with diminished accumulation of [Ca 2+ ] i in the vessel wall during H 2 O 2 exposure. In young mice, genetic deletion of IL-10 mimicked the protective effect of ageing on cell death and [Ca 2+ ] i accumulation. Whereas endothelial denudation or gap junction inhibition (carbenoxolone; 100 µM) increased SMC death, inhibiting NO synthase (L-NAME, 100 µM) or scavenging peroxynitrite (FeTPPS, 5 µM) reduced SMC death along with [Ca 2+ ] i . Despite NO toxicity via peroxynitrite formation, endothelial integrity protects SMCs. Caspase inhibition (Z-VAD-FMK, 50 µM) attenuated cell death with immunostaining for annex...

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Section: Methodsmentioning

confidence: 99%

Advanced age protects resistance arteries of mouse skeletal muscle from oxidative stress through attenuating apoptosis induced by hydrogen peroxide

Norton

Sinkler

Jacobsen

et al. 2019

The Journal of Physiology

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“…Excessive synthesis of reactive oxygen species (ROS) intensifies peroxynitrite formation, which disturbs endothelial nitric oxide synthase function and NO-mediated endothelial dilatation, resulting in hypertension [ 33 , 34 ]. Properly functioning mitochondria provide an efficient anti-oxidative system in the form of SOD and CAT activity, which prevents excessive ROS formation [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Diuretics, Ca-Antagonists, and Angiotensin-Converting Enzyme Inhibitors Affect Zinc Status in Hypertensive Patients on Monotherapy: A Randomized Trial

et al. 2018

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Background: Antihypertensive drugs affect mineral metabolism, inflammation, and the oxidative state. The aim of this study was to evaluate the effects of antihypertensive monopharmacotherapy with diuretics, β-blockers, calcium antagonists (Ca-antagonists), angiotensin-converting enzyme inhibitors (ACE-I), and angiotensin II receptor antagonists (ARBs) on zinc (Zn), iron (Fe), and copper (Cu) status, parameters of oxidative and inflammatory states, and glucose and lipid metabolism in patients with newly diagnosed primary arterial hypertension (AH). Methods: Ninety-eight hypertensive subjects received diuretics, β-blockers, Ca-antagonists, ACE-I, or ARB for three months. Zn, Fe, and Cu concentrations were determined in blood, urine, and hair. Results: A decrease in zinc serum and erythrocyte concentration and an increase in zinc urine concentration were registered after diuretic administration. Ca-antagonists led to a decrease in erythrocyte zinc concentration. A decrease in serum zinc concentration was observed after ACE-I. A decrease in triglyceride serum concentration was noted after ACE-I therapy, and a decrease in tumor necrosis factor-α serum concentration was seen following administration of Ca-antagonists. Hypotensive drugs led to decreases in catalase and superoxide dismutase serum concentrations. Conclusions: Three-months of monotherapy with diuretics, Ca-antagonists, or ACE-I impairs zinc status in patients with newly diagnosed primary AH. Antihypertensive monopharmacotherapy and zinc metabolism alterations affect lipid metabolism, the oxidative state, and the inflammatory state.

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“…Alterations in ER loading and the release of Ca 2+ are associated with aging. For example, in aged mice, stimulation with a neurotransmitter (acetylcholine) significantly increased the intracellular release of Ca 2+ from the ER [121]. Furthermore, aged cells with an interrupted Ca 2+ balance demonstrated an impaired ER response to stress conditions [122].…”

Section: Interorganellar Communicationmentioning

confidence: 99%

Cellular Aging Characteristics and Their Association with Age-Related Disorders

et al. 2020

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Different molecular signaling pathways, biological processes, and intercellular communication mechanisms control longevity and are affected during cellular senescence. Recent data have suggested that organelle communication, as well as genomic and metabolic dysfunctions, contribute to this phenomenon. Oxidative stress plays a critical role by inducing structural modifications to biological molecules while affecting their function and catabolism and eventually contributing to the onset of age-related dysfunctions. In this scenario, proteins are not adequately degraded and accumulate in the cell cytoplasm as toxic aggregates, increasing cell senescence progression. In particular, carbonylation, defined as a chemical reaction that covalently and irreversibly modifies proteins with carbonyl groups, is considered to be a significant indicator of protein oxidative stress and aging. Here, we emphasize the role and dysregulation of the molecular pathways controlling cell metabolism and proteostasis, the complexity of the mechanisms that occur during aging, and their association with various age-related disorders. The last segment of the review details current knowledge on protein carbonylation as a biomarker of cellular senescence in the development of diagnostics and therapeutics for age-related dysfunctions.

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Impact of Aging on Calcium Signaling and Membrane Potential in Endothelium of Resistance Arteries: A Role for Mitochondria

Cited by 28 publications

References 89 publications

Advanced age protects resistance arteries of mouse skeletal muscle from oxidative stress through attenuating apoptosis induced by hydrogen peroxide

Advanced age protects resistance arteries of mouse skeletal muscle from oxidative stress through attenuating apoptosis induced by hydrogen peroxide

Diuretics, Ca-Antagonists, and Angiotensin-Converting Enzyme Inhibitors Affect Zinc Status in Hypertensive Patients on Monotherapy: A Randomized Trial

Cellular Aging Characteristics and Their Association with Age-Related Disorders

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