CLIC4 localizes to mitochondrial-associated membranes and mediates cardioprotection

Ponnalagu, Devasena; Hamilton, Shanna; Sanghvi, Shridhar; Antelo, Diego; Schwieterman, Neill; Hansra, Inderjot; Xu, Xianyao; Gao, Erhe; Edwards, John C.; Bansal, Shyam S.; Wold, Loren E.; Terentyev, Dmitry; Janssen, Paul M.L.; Hund, Thomas J.; Khan, Mahmood; Kohut, Andrew; Koch, Walter J.; Singh, Harpreet

doi:10.1126/sciadv.abo1244

Cited by 20 publications

(14 citation statements)

References 58 publications

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“…Mitochondria are the regulatory center of cell apoptosis and the decrease of MMP is a hallmark event in the early stages of apoptosis. [ 34 ] In the process that mitochondria generate adenosine triphosphate via respiration to provide cellular energy, hydrogen ions (H + ) are pumped into the mitochondrial intermembrane space, thus there are large amounts of positive charges in the intermembrane space and negative charges in the matrix, forming the mitochondrial transmembrane potential. The piezoelectric potential and current generated by the sono‐piezoelectricity of MT‐MOF TNS could compromise MMP.…”

Section: Resultsmentioning

confidence: 99%

Bimetallic Organic Frameworks of High Piezovoltage for Sono‐Piezo Dynamic Therapy

et al. 2023

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Piezoelectric materials produce charges to directly act on cancer medium or promote reactive oxygen species (ROS) generation for novel tumor therapy triggered by sonography. Currently, piezoelectric sonosensitizers are mainly used to catalyze ROS generation by band‐tilting effect for sonodynamic therapy. However, it remains a challenge for piezoelectric sonosensitizers to produce high piezo‐voltages to overcome the band‐gap barrier for direct charge generation. Herein, the Mn‐Ti bimetallic organic framework tetragonal nanosheets (MT‐MOF TNS) are designed to produce high piezo‐voltages for novel sono‐piezo dynamic therapy (SPDT) with remarkable antitumor efficacy in vitro and in vivo. MT‐MOF TNS content non‐centrosymmetric secondary building units of Mn‐Ti‐oxo cyclic octamers with charge heterogeneous components for piezoelectricity. MT‐MOF TNS promote strong sono‐cavitation to insitu induce piezoelectric effect with a high sono‐piezo (SP) voltage (2.9 V) to directly excite charges, which is validated by sono‐piezo‐excited luminescence spectrometry. The SP voltage and charges depolarize the mitochondrial and plasma membrane potentials, and cause ROS overproduction and serious tumor cell damage. Importantly, MT‐MOF TNS can be decorated with targeting molecules and chemotherapeutics for more severe tumor regression by combining SPDT with chemodynamic therapy and chemotherapy. This report develops a fascinating MT‐MOF piezoelectric nano‐semiconductor and provides an efficient SPDT strategy for tumor treatment.This article is protected by copyright. All rights reserved

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Section: Resultsmentioning

confidence: 99%

Bimetallic Organic Frameworks of High Piezovoltage for Sono‐Piezo Dynamic Therapy

et al. 2023

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“…To assess the infarct size, ImageJ software (NIH) was utilized for measurement, where the TTC-negative area (pan) represented the infarcted myocardium, and the TTC-stained area appeared red. Myocardial infarct size was presented as a proportion of total left ventricular area expressed as a percentage …”

Section: Methodsmentioning

confidence: 99%

“…Myocardial infarct size was presented as a proportion of total left ventricular area expressed as a percentage. 61 Masson's Trichrome Staining. For Masson's trichrome staining, paraffin-embedded heart slices were dewaxed and rehydrated using an ethanol gradient.…”

Section: Synthesis Of Chomentioning

confidence: 99%

One Endothelium-Targeted Combined Nucleic Acid Delivery System for Myocardial Infarction Therapy

Shao,

Xu,

Zhu

et al. 2024

ACS Nano

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Acute myocardial infarction (MI) and ischemic heart disease are the leading causes of heart failure and mortality. Currently, research on MI treatment is focused on angiogenic and anti-inflammatory therapies. Although endothelial cells (ECs) are critical for triggering inflammation and angiogenesis, no approach has targeted them for the treatment of MI. In this study, we proposed a nonviral combined nucleic acid delivery system consisting of an EC-specific polycation (CRPPR-grafted ethanolamine-modified poly(glycidyl methacrylate), CPC) that can efficiently codeliver siR-ICAM1 and pCXCL12 for the treatment of MI. Animals treated with the combination therapy exhibited better cardiac function than those treated with each nucleic acid alone. In particular, the combination therapy of CPC/siR-ICAM1 and CPC/pCXCL12 significantly improved cardiac systolic function, anti-inflammatory responses, and angiogenesis compared to the control group. In conclusion, CPC-based combined gene delivery systems show impressive performance in the treatment of MI and provide a programmed strategy for the development of codelivery systems for various EC-related diseases.

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“…Indeed, mCa 2 + overload due to disruption of ERmitochondria crosstalk in the MAM domain is implicated in the formation of the deleterious and permanent mitochondrial permeability transition pore (mPTP) opening and CM death [92,93,96,97]. Deleterious mPTP opening following oxidative stress, mCa 2 + overload or combination of both, has been reported as a trigger for IR injury or AMI [92,[98][99][100][101]. As alluded to previously, it is well known that the benefits of TRN encompass adaptations in heart and CM function as well as other systems that have secondary beneficial effects on cardiac efficiency [3,10,102,103].…”

Section: Importance Of Mitochondria Associated Membrane and Its Role ...mentioning

confidence: 99%

Cardiomyocyte Adaptation to Exercise: K+ Channels, Contractility and Ischemic Injury

Fitts,

Wang,

Kwok

et al. 2024

Int J Sports Med

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Cardiovascular disease is a leading cause of morbidity and mortality, and exercise-training (TRN) is known to reduce risk factors and protect the heart from ischemia and reperfusion injury. Though the cardioprotective effects of exercise are well-documented, underlying mechanisms are not well understood. This review highlights recent findings and focuses on cardiac factors with emphasis on K+ channel control of the action potential duration (APD), β-adrenergic and adenosine regulation of cardiomyocyte function, and mitochondrial Ca2+ regulation. TRN-induced prolongation and shortening of the APD at low and high activation rates, respectively, is discussed in the context of a reduced response of the sarcolemma delayed rectifier potassium channel (IK) and increased content and activation of the sarcolemma KATP channel. A proposed mechanism underlying the latter is presented, including the phosphatidylinositol-3kinase/protein kinase B pathway. TRN induced increases in cardiomyocyte contractility and the response to adrenergic agonists are discussed. The TRN-induced protection from reperfusion injury is highlighted by the increased content and activation of the sarcolemma KATP channel and the increased phosphorylated glycogen synthase kinase-3β, which aid in preventing mitochondrial Ca2+ overload and mitochondria-triggered apoptosis. Finally, a brief section is presented on the increased incidences of atrial fibrillation associated with age and in life-long exercisers.

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CLIC4 localizes to mitochondrial-associated membranes and mediates cardioprotection

Cited by 20 publications

References 58 publications

Bimetallic Organic Frameworks of High Piezovoltage for Sono‐Piezo Dynamic Therapy

Bimetallic Organic Frameworks of High Piezovoltage for Sono‐Piezo Dynamic Therapy

One Endothelium-Targeted Combined Nucleic Acid Delivery System for Myocardial Infarction Therapy

Cardiomyocyte Adaptation to Exercise: K+ Channels, Contractility and Ischemic Injury

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