Mitochondrial membrane potential instability on reperfusion after ischemia does not depend on mitochondrial Ca2+ uptake

Ashok, Deepthi; Papanicolaou, Kyriakos N.; Sidor, Agnieszka; Wang, Michelle; Solhjoo, Soroosh; Liu, Ting; O’Rourke, Brian

doi:10.1016/j.jbc.2023.104708

Cited by 14 publications

(6 citation statements)

References 80 publications

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“…The loss of ΔΨm is a hallmark of hypoxia-reperfusion injury that results in cell death (Ashok et al, 2023; Weinberg et al, 2000). ΔΨm, measured with TMRE, revealed that N2a cells exposed to hypoxia-reperfusion had a lower ΔΨm compared to the untreated control (Fig.…”

Section: Resultsmentioning

confidence: 99%

The Neuroprotective Effect of Short-chain Fatty Acids Against Hypoxia-reperfusion Injury

Harijan,

Kalaiarasan,

Ghosh

et al. 2023

Preprint

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Gut microbe-derived short-chain fatty acids (SCFAs) are known to have a profound impact on various brain functions, including cognition, mood, and overall neurological health. However, their role, if any, in protecting against hypoxic injury and ischemic stroke has not been extensively studied. In this study, we investigated the effects of two major SCFAs abundant in the gut, propionate (P) and butyrate (B), on hypoxia-reperfusion injury using a neuronal cell line and a zebrafish model. Neuro 2a (N2a) cells treated with P and B exhibited reduced levels of mitochondrial and cytosolic reactive oxygen species (ROS), diminished loss of mitochondrial membrane potential, suppressed caspase activation, and lower rates of cell death when exposed to CoCl2-induced hypoxia, compared to the control group. Furthermore, adult zebrafish fed with SCFAs-supplemented feeds showed less susceptibility to hypoxic conditions compared to the control group, as indicated by multiple behavioral measures. Histological analysis of TTC-stained brain sections revealed lesser damage in the SCFAs-fed group. We also found that FABP7 (also known as BLBP), a neuroprotective fatty acid binding protein, was upregulated in the brains of the SCFAs-fed group. Additionally, when FABP7 was overexpressed in N2a cells, it protected the cells from hypoxia-reperfusion injury. Overall, our data clearly demonstrates a neuroprotective role of P and B against hypoxic brain injury and suggests the potential of dietary supplementation with SCFAs to mitigate stroke-induced brain damage.HighlightsShort-chain fatty acid (SCFA) Propionate (P) and Butyrate (B) protect N2a cells from hypoxia-reperfusion.Zebrafish, when fed an SCFA-supplemented diet, are more resilient to hypoxia-reperfusion.SCFAs in the diet boost brain expression of FABP7 (fatty acid binding protein).FABP7 overexpression in N2a cells provides protection against hypoxia-reperfusion.SCFAs reduce reactive oxygen species (ROS) levels and increase FABP7, contributing to neuroprotection.

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Section: Resultsmentioning

confidence: 99%

The Neuroprotective Effect of Short-chain Fatty Acids Against Hypoxia-reperfusion Injury

Harijan,

Kalaiarasan,

Ghosh

et al. 2023

Preprint

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“…It is still debated whether Ca 2+ overload is mediated by Ca 2+ uptake via the MCU or by the mitochondrial NCX, which represents the primary Ca 2+ efflux pathway under physiological conditions ( Fig. 11 ), operating in reverse mode during ischemia and the early phase of reperfusion [ 394 ]. Mitochondrial Ca 2+ overload partly dissipates the proton motive force and, above a certain threshold, triggers PTP opening, in particular in combination with oxidative stress [ 392 , 395 ].…”

Section: Sources and Actions Of Reactive Oxygen Speciesmentioning

confidence: 99%

“…Upon reperfusion, succinate is rapidly oxidized by SDH, driving reverse electron transport and extensive superoxide production at complex I [ 52 ]. Mitochondrial ROS production induces mitochondrial membrane instability and sensitizes to PTP opening [ 394 ]. Furthermore, the burst of ROS during reperfusion of ischemic myocardium causes cytosolic Ca 2+ overload and myocardial “stunning”, which is characterized by diastolic and systolic dysfunction that is - at least to some extent – reversible [ 182 , 397 ].…”

Section: Sources and Actions Of Reactive Oxygen Speciesmentioning

confidence: 99%

Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection

Heusch,

Andreadou,

Bell

et al. 2023

Redox Biology

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“…Overexpression of MCUR1 promotes calcium uptake by the mitochondria [162]. The mtCU dysfunction plays an essential role in several diseases, such as cancer, Parkinson's disease, and cardiovascular pathologies, including ischemia/reperfusion and pulmonary arterial hypertension [169][170][171][172][173]. Targeting the uniporter for the treatment of diseases related to the dysfunction of the mtCU has a significant translational potential for a novel therapy in particular cardiovascular diseases [168].…”

Section: Sodium-calcium Exchangersmentioning

confidence: 99%

Calcium Homeostasis, Transporters, and Blockers in Health and Diseases of the Cardiovascular System

Bkaily

Jacques

2023

IJMS

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Calcium is a highly positively charged ionic species. It regulates all cell types’ functions and is an important second messenger that controls and triggers several mechanisms, including membrane stabilization, permeability, contraction, secretion, mitosis, intercellular communications, and in the activation of kinases and gene expression. Therefore, controlling calcium transport and its intracellular homeostasis in physiology leads to the healthy functioning of the biological system. However, abnormal extracellular and intracellular calcium homeostasis leads to cardiovascular, skeletal, immune, secretory diseases, and cancer. Therefore, the pharmacological control of calcium influx directly via calcium channels and exchangers and its outflow via calcium pumps and uptake by the ER/SR are crucial in treating calcium transport remodeling in pathology. Here, we mainly focused on selective calcium transporters and blockers in the cardiovascular system.

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Mitochondrial membrane potential instability on reperfusion after ischemia does not depend on mitochondrial Ca2+ uptake

Cited by 14 publications

References 80 publications

The Neuroprotective Effect of Short-chain Fatty Acids Against Hypoxia-reperfusion Injury

The Neuroprotective Effect of Short-chain Fatty Acids Against Hypoxia-reperfusion Injury

Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection

Calcium Homeostasis, Transporters, and Blockers in Health and Diseases of the Cardiovascular System

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