Review
Chemistry, Multidisciplinary
Daniel Khananshvili
Summary: The superfamily of Calcium/Cation (Ca2+/CA) antiporters play a crucial role in ion transport and selectivity, with shared structural motifs but unclear dynamic determinants. The archaeal Na+/Ca2+ exchanger (NCX_Mj) is proposed as a structural model to investigate ion transport mechanisms, highlighting the importance of ion-coordinating residues and ion-permeating helices in the process. This research may provide insights into the structure-dynamic and functional aspects of ion-coupled transport in Ca2+/CA proteins.
FRONTIERS IN CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Hanxing Wan, Nannan Gao, Wei Lu, Cheng Lu, Jun Chen, Yimin Wang, Hui Dong
Summary: This study found that increased expression of NCX1 and TRPC1 is associated with tumor progression and decreased survival in human gastric cancer. Through functional coupling, TRPC1 drives NCX1 into the calcium entry mode, leading to elevated cytosolic calcium levels in gastric cancer cells. H. pylori and its virulence factors enhance the expressions and activities of NCX1 and TRPC1, promoting proliferation, migration, and invasion of gastric cancer cells through the AKT/beta-catenin pathway.
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
Chemistry, Medicinal
Huiting Xia, Aqeela Zahra, Meng Jia, Qun Wang, Yunfu Wang, Susan L. Campbell, Jianping Wu
Summary: In this review, the potential role of NHE1 in cardiac hypertrophy and heart failure is discussed, along with an investigation into the underlying molecular mechanisms.
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.
Article
Multidisciplinary Sciences
Jing Xue, Weizhong Zeng, Yan Han, Scott John, Michela Ottolia, Youxing Jiang
Summary: In this study, the cryo-EM structures of human cardiac NCX1 were presented, elucidating key structural elements for ion exchange and modulation by cytosolic Ca2+ and Na+.
NATURE COMMUNICATIONS
(2023)
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
Cell Biology
Caglar Gok, Alan D. Robertson, William Fuller
Summary: In this study, we found that insulin regulates the activity of NCX1 by inducing its palmitoylation, thereby modulating Ca2+ handling in cardiac cells. By activating fatty acid and fatty acyl CoA synthesis, insulin promotes palmitoylation of the zDHHC5 active site, leading to enhanced NCX1 palmitoylation.
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
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
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
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)
Article
Pharmacology & Pharmacy
Ilaria Piccialli, Roselia Ciccone, Agnese Secondo, Francesca Boscia, Valentina Tedeschi, Valeria de Rosa, Pasquale Cepparulo, Lucio Annunziato, Anna Pannaccione
Summary: The activity of NCX, especially the NCX3 isoform, was found to be upregulated in AD neurons, contributing to an increase in ER Ca2+ content while not affecting cytosolic Ca2+ concentrations. Functional coupling between NCX3 and the voltage-gated Na(V)1.6 channels was uncovered, suggesting a potential role of NCX3 in the Ca2+ remodelling of AD neurons.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jesse A. Stokum, Bosung Shim, Serban Negoita, Natalya Tsymbalyuk, Orest Tsymbalyuk, Svetlana Ivanova, Kaspar Keledjian, Joseph Bryan, Mordecai P. Blaustein, Ruchira M. Jha, Kristopher T. Kahle, Volodymyr Gerzanich, J. Marc Simard
Summary: Brain swelling, caused by water influx into perivascular astrocytes through aquaporins, can be reduced by targeting channels in astrocyte endfeet. In a mouse model of severe ischemic stroke, the abundance of SUR1-TRPM4 and NCX1 in perivascular astrocytic endfeet was increased, leading to the translocation of AQP4 to the plasma membrane and subsequent water accumulation, resulting in cellular edema and brain swelling. Inhibition or deletion of SUR1-TRPM4 or NCX1 reduced brain swelling and improved neurological function in mice, independent of infarct size.
Article
Biochemistry & Molecular Biology
Zikai Liu, Qing Cheng, Xiaoli Ma, Mingke Song
Summary: Pharmacological modulation of the Na+/Ca2+ exchanger (NCX) can suppress melanoma cells and induce cell death, making NCX a potential drug target for cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)