Regulation of Calcium Homeostasis by ER Redox: A Close-Up of the ER/Mitochondria Connection

Yang

et al. 2018

Cell Physiol Biochem

Background/Aims: Total saponins of Aralia elata (Miq) Seem (AS) from the Chinese traditional herb Long ya Aralia chinensis L. reportedly provide cardioprotective effects, but the exact mechanisms require further study. Previous studies have showed that myocardial ischemia/ reperfusion injury (MIRI) was related to calcium homeostasis imbalance and endoplasmic reticulum stress (ERS). Thus, this study aimed to demonstrate protective effects of AS on MIRI. Methods: After administrating AS for 5 days, the left anterior descending artery coronary artery of Sprague-Dawley (SD) rats was ligated for 30 min. After 48 h of reperfusion, haemodynamics, Evans blue/ 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, masson staining and the levels of lactate dehydrogenase (LDH) and creatine kinase (CK), superoxide dismutase (SOD), malondialdehyde (MDA) were detected to assess MIRI. ATPase activity and Western Blot were used to study the mechanisms. Results: Compared with IR group, AS treatment groups could significantly reduce myocardial infarct size; improve myocardial pathologic progress; decrease content of LDH, CK, and MDA; increase content of SOD; and restore the activities of Ca²⁺-Mg²⁺-ATPase, Na⁺-K⁺-ATPase, sarcoplasmic reticulum Ca²⁺-ATPases (SERCA), and calcineurin (CaN). AS treatment groups also significantly up-regulated the expression of GRP78, C/EBP homologous protein (CHOP), and Bax, and down-regulated the expression of Bcl-2, all similar to the effects of ERS. Conclusion: These findings illustrated that AS could prevent myocardial ischemia/reperfusion injury and reduce calcium homeostasis imbalance and ERS-related apoptosis.

Section: Discussionmentioning

confidence: 99%

Total Saponins of Aralia Elata (Miq) Seem Alleviate Calcium Homeostasis Imbalance and Endoplasmic Reticulum Stress-Related Apoptosis Induced by Myocardial Ischemia/Reperfusion Injury

Yang

et al. 2018

Cell Physiol Biochem

Clinical Transplantation

“…Under cold storage conditions, oxidative stress arises because of the release of catalytic iron from cytochrome P450 degradation . The accumulation of ROS leads to an increased release of calcium ions from intracellular stores and from the extracellular environment via store‐operated channels . A vicious circle gets started because intracellular calcium homeostasis depends on high‐energy phosphates to maintain the mitochondrial membrane potential.…”

Section: Molecular Mechanisms Of Protectionmentioning

confidence: 99%

“…This results in oxidative stress and concomitant depletion of glutathione ( GSH ). Ryanodine receptors in the endoplasmic reticulum become activated as consequence of low GSH , thereby releasing calcium into the cytoplasm . This in turn initiates the influx of extracellular calcium into the cell via store‐operated channels.…”

Section: Molecular Mechanisms Of Protectionmentioning

confidence: 99%

“…29,30 The accumulation of ROS leads to an increased release of calcium ions from intracellular stores and from the extracellular environment via store-operated channels. 31,32 A vicious circle gets started because intracellular calcium homeostasis depends on high-energy phosphates to maintain the mitochondrial membrane potential. While hypothermia lowers the synthesis of adenosine triphosphate (ATP) on the one hand, the influx of calcium On dialysis GFR≤25 GFR>25 p = 0.008 p = 0.01 further exhausts ATP on the other.…”

Section: Molecul Ar Mechanis Ms Of Protec Ti Onmentioning

confidence: 99%

“…Ryanodine receptors in the endoplasmic reticulum become activated as consequence of low GSH, thereby releasing calcium into the cytoplasm. 32 This in turn initiates the influx of extracellular calcium into the cell via store-operated channels. Oxidative stress may also facilitate calcium entry via direct effects on the cell membrane.…”

Section: Effec T On the Performan Ce Of Non -Renal G R Af Tsmentioning

confidence: 99%

See 2 more Smart Citations

Dopamine in transplantation: Written off or comeback with novel indication?

Schnuelle¹,

Benck

Yard

2018

Renal-dose dopamine has fallen out of favor in the intensive care unit (ICU) during past years due to its ineffectiveness to prevent impending or to ameliorate overt renal failure in the critically ill. By contrast, growing evidence indicates that low-dose dopamine administered to the stable organ donor after brain death confirmation improves the clinical course of transplanted organs after kidney and heart transplantation. Ensuring a thorough monitoring for potential circulatory side effects, employment of dopamine at a dose of 4 μg/kg/min is safe in the deceased donor. Among recipients, the advantageous effect is easy to achieve, inexpensive, and devoid of adverse side effects. The mode of action relies on dopamine's propensity to mitigate injury in various cell systems from isolated transplantable organs under cold storage conditions. The present review article summarizes the clinical evidence of dopamine donor pretreatment in solid organ transplantation and focuses on the underlying molecular mechanisms of cellular protection. Introducing the routine use of low-dose dopamine for the management of the brain-dead donor in the ICU before procurement provides an evidence-based strategy to improve graft outcome after kidney transplantation without conferring harm to non-renal grafts, namely to livers and hearts, in cases of multi-organ donation.

Journal of Biophotonics

Continuous assessment of metabolic activity of mitochondria using resonance Raman microspectroscopy

Lalonde

Noojin²,

Pope³

et al. 2021

Dysfunctional mitochondrial activity can lead to a variety of different diseases. As such, there exists a need to quantify changes in mitochondria function as it relates to these specific diseased states. Here, we present the use of resonance Raman (RR) spectroscopy as a tool to determine changes in isolated mitochondrial activity. RR spectroscopy, using 532 nm as the excitation source, specifically provides information on the reduction and oxidation (RedOx) state of cytochrome c, which is determined by the activity of protein complexes in the electron transport chain (ETC). In this model, injection of the substrate succinate into the mitochondrial sample is used to drive the ETC, which causes a subsequent change in cytochrome c RedOx state. This change in RedOx state is tracked by RR spectroscopy. This tool gives real‐time information on the rise and fall of the amount of reduced cytochrome c within the mitochondrial sample, providing a method for rapid assessment of mitochondrial metabolism that has broad applications in both basic science and medical research.