Cardioprotective Effect against Ischemia–Reperfusion Injury of PAK-200, a Dihydropyridine Analog with an Inhibitory Effect on Cl− but Not Ca2+ Current DOI Creative Commons

Iyuki Namekata,

Miku Tamura,

Jyunya Kase

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(12), P. 1719 - 1719

Published: Nov. 29, 2023

We examined the effects of a dihydropyridine analog, PAK-200, on guinea pig myocardium during experimental ischemia and reperfusion. In isolated ventricular cardiomyocytes, PAK-200 (1 μM) had no effect basal peak inward steady-state currents but inhibited isoprenaline-induced time-independent Cl− current. right atria, beating rate chronotropic response to isoprenaline. an ischemia–reperfusion model with coronary-perfused tissue, decrease in contractile force rise tension were observed period 30-min no-flow ischemia. Upon reperfusion, returned less than 50% preischemic values. decline reduced resting tension. significantly improved recovery after reperfusion about 70% value. was also shown attenuate tissue ATP Treatment myocytes ischemia-mimetic solution resulted depolarization mitochondrial membrane potential increase cytoplasmic Ca2+ concentrations. delayed these changes. Thus, inhibits cAMP-activated chloride current cardiac muscle may have protective against injury through novel mechanisms.

Language: Английский

Rhodiola crenulata alleviates hypobaric hypoxia-induced brain injury by maintaining BBB integrity and balancing energy metabolism dysfunction DOI

Ya Hou,

Fuhan Fan,

Na Xie

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 128, P. 155529 - 155529

Published: March 11, 2024

Language: Английский

Citations

32
Functional interplay of lipid droplets and mitochondria DOI Open Access
Ludovic Enkler, Anne Spang

FEBS Letters, Journal Year: 2024, Volume and Issue: 598(10), P. 1235 - 1251

Published: Jan. 24, 2024

Our body stores energy mostly in form of fatty acids (FAs) lipid droplets (LDs). From there the FAs can be mobilized and transferred to peroxisomes mitochondria. This transfer is dependent on close opposition LDs mitochondria happens at membrane contact sites. However, composition dynamics these sites not well understood, which part due dependence metabolic state cell cell- tissue-type. Here, we summarize current knowledge contacts between both mammals yeast Saccharomyces cerevisiae, various are studied. We discuss possible functions site their implication disease.

Language: Английский

Citations

14
ER-mitochondria distance is a critical parameter for efficient mitochondrial Ca2+ uptake and oxidative metabolism DOI Creative Commons
Giulia Dematteis, Laura Tapella, Claudio Casali

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Oct. 10, 2024

IP

Language: Английский

Citations

13
Mitochondrial Calcium Regulation of Cardiac Metabolism in Health and Disease DOI
Enrique Balderas, Sandra Lee, Neeraj Kumar Vasistha

et al.

Physiology, Journal Year: 2024, Volume and Issue: 39(5), P. 247 - 268

Published: May 7, 2024

Oxidative phosphorylation is regulated by mitochondrial calcium (Ca2+) in health and disease. In physiological states, Ca2+ enters via the uniporter rapidly enhances NADH ATP production. However, maintaining homeostasis critical: insufficient impairs stress adaptation, overload can trigger cell death. this review, we delve into recent insights further defining relationship between dynamics oxidative phosphorylation. Our focus on how such regulation affects cardiac function disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, cardiomyopathies, Barth syndrome, Friedreich's ataxia. Several themes emerge from data. First, critical for fuel substrate selection, metabolite import, matching of supply to demand. Second, regulates both production response reactive oxygen species (ROS), balance its pro- antioxidant effects key it contributes pathological states. Third, exerts localized electron transport chain (ETC), not through traditional allosteric mechanisms but rather indirectly. These hinge specific transporters, as or Na+/Ca2+ exchanger, may be noticeable acutely, contributing differently phenotypes depending whether transporters are acutely chronically modified. Perturbations these novel relationships during disease states either serve compensatory exacerbate impairments Consequently, targeting holds promise a therapeutic strategy variety diseases characterized contractile failure arrhythmias.

Language: Английский

Citations

10
Cognitive impairment caused by compromised hepatic ketogenesis is prevented by endurance exercise DOI Open Access
Taylor J. Kelty, Nathan R. Kerr, Chien-Chih Chou

et al.

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract Extensive research has demonstrated endurance exercise to be neuroprotective. Whether these neuroprotective benefits are mediated, in part, by hepatic ketone production remains unclear. To investigate the role of on brain health during exercise, healthy 6‐month‐old female rats underwent viral knockdown rate‐limiting enzyme liver that catalyses first reaction ketogenesis: 3‐hydroxymethylglutaryl‐CoA synthase 2 (HMGCS2). Rats were then subjected either a bout acute or 4 weeks chronic treadmill running (5 days/week) and cognitive behavioural testing. Acute elevated plasma concentration 1 h following exercise. Hepatic HMGCS2 knockdown, verified protein expression, reduced after 48 Proteomic analysis enrichment frontal cortex revealed markers mitochondrial function significantly state 3 complex I + II respiration isolated mitochondria from Spatial memory synaptic plasticity knockdown. These deficiencies prevented training. In summary, data propose ketogenesis is required maintain cognition function, irrespective training status, can overcome neuropathology caused insufficient ketogenesis. results establish mechanistic link between enhance our understanding how peripheral tissue metabolism influences health. image Key points Decades literature demonstrate This study provides set suggest cognition, function. indicate protect against decline compromised prompting further investigation

Language: Английский

Citations

1
Unravelling the complexity of the mitochondrial Ca2+ uniporter: regulation, tissue specificity, and physiological implications DOI Creative Commons
Denis Vecellio Reane, Julian D. C. Serna, Anna Raffaello

et al.

Cell Calcium, Journal Year: 2024, Volume and Issue: 121, P. 102907 - 102907

Published: May 23, 2024

Calcium (Ca

Language: Английский

Citations

5
High-Throughput Identification of Calcium Regulated Proteins Across Diverse Proteomes DOI Creative Commons
Timothy M. Locke, Rose Fields,

Hayden Gizinski

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 18, 2024

Calcium ions play important roles in nearly every biological process, yet whole-proteome analysis of calcium effectors has been hindered by lack high-throughput, unbiased, and quantitative methods to identify proteins-calcium engagement. To address this, we adapted protein thermostability assays the budding yeast, human cells, mouse mitochondria. Based on calcium-dependent thermostability, identified 2884 putative calcium-regulated proteins across human, mouse, yeast proteomes. These data revealed engagement novel signaling hubs cellular processes, including metabolic enzymes spliceosome. Cross-species comparison calcium-protein mutagenesis experiments residue-specific cation engagement, even within well-known EF-hand domains. Additionally, found that dienoyl-CoA reductase DECR1 binds at physiologically-relevant concentrations with substrate-specific affinity, suggesting direct regulation mitochondrial fatty acid oxidation. proteomic analyses establish a key resource dissect its mechanistic effects multiple species diverse processes.

Language: Английский

Citations

4
Antimicrobial cetylpyridinium chloride causes functional inhibition of mitochondria as potently as canonical mitotoxicants, nanostructural disruption of mitochondria, and mitochondrial Ca2+ efflux in living rodent and primary human cells DOI Creative Commons

Sasha R. Weller,

John E. Burnell,

Brandon M. Aho

et al.

Food and Chemical Toxicology, Journal Year: 2024, Volume and Issue: 186, P. 114547 - 114547

Published: Feb. 24, 2024

Language: Английский

Citations

4
Combined microbiomic and transcriptomic analysis revealed that dietary Clostridium autoethanogenum protein could improve the disease resistance of Litopenaeus vannamei by regulating the oxidative phosphorylation DOI
Lili Shi, Xiaobo Yan, Yan Zhao

et al.

Aquaculture Reports, Journal Year: 2025, Volume and Issue: 41, P. 102687 - 102687

Published: Feb. 21, 2025

Language: Английский

Citations

0
Metabolic reprogramming in cancer and senescence DOI Creative Commons
Yuzhu Zhang, J. Tang, Can Jiang

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

The rising trend in global cancer incidence has caused widespread concern, one of the main reasons being aging population. Statistical data show that and mortality rates a clear upward with age. Although there is commonality between dysregulated nutrient sensing, which features aging, metabolic reprogramming tumor cells, specific regulatory relationship not clear. This manuscript intends to comprehensively analyze senescence reprogramming; as well reveal impact key factors leading cellular on tumorigenesis. In addition, this review summarizes current intervention strategies targeting sensing pathways, clinical cases treating tumors characteristics existing nanodelivery research strategies. Finally, it also suggests sensible dietary habits for those who wish combat aging. conclusion, attempts sort out link metabolism provide new ideas treatment.

Language: Английский

Citations

0