Article
Biochemistry & Molecular Biology
Hua-Wei Sun, Xiang-Ping Chu, Roger P. Simon, Zhi-Gang Xiong, Tian-Dong Leng
Summary: This study identifies a new ASIC inhibitor, KB-R7943, which has broad inhibitory effects and could be used to study the functions of ASIC channels and potentially develop treatments for ASIC-related disorders.
Article
Biochemistry & Molecular Biology
Pi-Cheng Cheng, Ruo-Ciao Cheng, Rong-Chi Huang
Summary: Glutamate induces Ca2+ signaling in the suprachiasmatic nucleus (SCN) by activating intracellular mechanisms involving Na+ loads, Na+/K+-ATPase (NKA), and Na+/Ca2+-exchanger (NCX). The presence of Na+ loads leads to slower Ca2+ clearance and increased rebound Ca2+ suppression. However, even in the absence of external Na+, additional Ca2+ handlers are involved in the slower Ca2+ clearance induced by glutamate.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ayako Takeuchi, Satoshi Matsuoka
Summary: The gene SLC24A6/SLC8B1 has been identified as the responsible gene for mitochondrial Na+-Ca2+ exchange for over 10 years, leading to a deeper understanding of the structure-function relationships and physiological/pathophysiological contributions of NCLX. Recent achievements regarding NCLX, focusing on its heart-specific characteristics, biophysical properties, spatial distribution in cardiomyocytes, and roles in cardiac functions under physiological and pathophysiological conditions, have been summarized in this review.
Article
Biochemistry & Molecular Biology
Sheng-Nan Wu, Meng-Cheng Yu
Summary: KB-R7943 is an isothiourea derivative that has been identified as an inhibitor of the Na+-Ca2+ exchange process in the reverse mode. This compound has been shown to prevent intracellular Na+-dependent Ca2+ uptake, but is less effective at preventing extracellular Na+-dependent Ca2+ efflux. Further studies are needed to determine whether and how KB-R7943 may affect other types of ionic currents, particularly the voltage-gated Na+ current (I-Na). This study demonstrates that KB-R7943 concentration-dependently depresses the transient (I-Na(T)) or late component (I-Na(L)) of I-Na, and has the potential to perturb the magnitude and gating kinetics of several other Na+ currents (I-Na(W), I-Na(R), and I-Na(P)).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Martin John Lewis, Igor Khaliulin, Katie Hall, M. Saadeh Suleiman
Summary: This study investigates the effectiveness of cardioprotective intervention in immature hearts and explores the involvement of the mitochondrial permeability transition pore (MPTP). The results demonstrate that immature hearts have a higher innate resistance to ischemia-reperfusion (I/R) injury compared to adult hearts, due to a reduced tendency of MPTP opening following reperfusion. Additionally, simultaneous activation of protein kinase A (PKA) and exchange protein activated by cAMP (Epac) provides cardioprotection that is additive to the innate resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Chenxia Hu, Lingfei Zhao, Fen Zhang, Lanjuan Li
Summary: The liver is the only organ with regenerative capacity, but various injury factors can lead to irreversible liver dysfunction. Liver resection and transplantation are effective treatments for liver failure. Melatonin has antioxidant properties and can attenuate liver ischemia/reperfusion injury. Understanding the mechanisms of melatonin's interactions with other cellular processes can improve its potential for treating liver diseases.
CELL PROLIFERATION
(2021)
Article
Biochemistry & Molecular Biology
Philipp Hegner, Marzena Drzymalski, Alexander Biedermann, Bernadette Memmel, Melanie Durczok, Michael Wester, Bernhard Floerchinger, Zdenek Provaznik, Christof Schmid, York Zausig, Lars S. Maier, Stefan Wagner
Summary: The novel selective NCX-inhibitor SAR296968 inhibits atrial pro-arrhythmic activity and improves diastolic and contractile function in human atrial myocardium, which may have therapeutic implications, especially for treatment of HFpEF.
Review
Pharmacology & Pharmacy
Tiago Rodrigues, Silvia Piccirillo, Simona Magi, Alessandra Preziuso, Vyctoria dos Santos Ramos, Tiziano Serfilippi, Monia Orciani, Marcela Maciel Palacio Alvarez, Ivarne Luis dos Santos Tersariol, Salvatore Amoroso, Vincenzo Lariccia
Summary: Spatial and temporal control of calcium levels is crucial for cell activities. Na+/Ca2+ exchangers (NCXs) play a role in maintaining calcium homeostasis and supporting cellular metabolism. Preserving a timed and balanced NCX activity has therapeutic potential for various diseases.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Simon Thibault, Valerie Long, Celine Fiset
Summary: Male sex is a significant risk factor for atrial fibrillation (AF), with a higher incidence in men. This study demonstrates major sex differences in intracellular Ca2+ homeostasis in mouse atrial myocytes, including larger Ca2+ transients, enhanced Na+-Ca2+ exchanger (NCX1) function and expression, and more frequent spontaneous Ca2+ releases in males. These differences may contribute to the higher susceptibility of males to AF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Noor Nadhim Al-Saigh, Shtaywy Abdalla
Summary: This study found that safranal induces vasodilation through the inhibition of calcium influx from extracellular space through L-type Ca2+ channels and the inhibition of Na+/Ca2+ exchanger.
Article
Cardiac & Cardiovascular Systems
Hiran A. Prag, Anja Gruszczyk, Margaret M. Huang, Timothy E. Beach, Timothy Young, Laura Tronci, Efterpi Nikitopoulou, John F. Mulvey, Raimondo Ascione, Anna Hadjihambi, Michael J. Shattock, Luc Pellerin, Kourosh Saeb-Parsy, Christian Frezza, Andrew M. James, Thomas Krieg, Michael P. Murphy, Dunja Aksentijevic
Summary: Release of accumulated succinate in the ischaemic heart upon reperfusion is mediated by MCT1 and is facilitated by acidification of the myocardium during ischaemia.
CARDIOVASCULAR RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Gen L. Takei, Yuhei Ogura, Yoshihiro Ujihara, Fubito Toyama, Keitaro Hayashi, Tomoe Fujita
Summary: Previous studies have shown that extracellular Na+ suppresses hamster sperm hyperactivation by reducing intracellular Ca2+ levels, and this suppressive effect can be canceled by specific inhibitors of Na+/Ca2+-exchanger (NCX). However, direct evidence of the presence and functionality of NCX in hamster spermatozoa is lacking. This study demonstrates the presence of functional NCX1 in hamster spermatozoa and its downregulation upon capacitation to trigger hyperactivation, providing novel insights into the regulation of sperm hyperactivation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Jinliang Nan, Jiamin Li, Yinuo Lin, Muhammad Saif Ur Rahman, Zhengzheng Li, Lingjun Zhu
Summary: Store-operated Ca2+ entry (SOCE) machinery and mitochondria are crucial for cellular calcium homeostasis and play key roles in cardiac diseases. They interact reciprocally and are involved in processes such as cardiac hypertrophy, diabetic cardiomyopathy, and cardiac ischaemia-reperfusion injury.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Medicine, Research & Experimental
O. A. Afolabi, D. C. Anyogu, M. A. Hamed, A. F. Odetayo, D. H. Adeyemi, R. E. Akhigbe
Summary: This study demonstrated for the first time that glutamine administration improved testicular ischemia/reperfusion injury in a torsion/detorsion rat model by maintaining testicular redox balance, and testicular integrity and function via inhibition of ischemia/reperfusion-induced upregulation of NF-kB signaling and caspase 3 activation.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Immunology
Jose R. Lopez, Nancy Linares, Jose A. Adams, Alfredo Mijares
Summary: Chagas disease is a leading cause of death and morbidity in Latin America, and this study reveals that chronic elevation of diastolic Ca2+ concentration is associated with the disease. The role of Na+/Ca2+ exchanger (NCX) in this process is also explored, suggesting that inhibitors of NCX may be a potential therapeutic approach for Chagas cardiomyopathy.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)