Article
Physiology
Lianguo Wang, Rachel C. Myles, I-Ju Lee, Donald M. Bers, Crystal M. Ripplinger
Summary: The study demonstrates that inhibition of SERCA can slow down SR Ca2+ reuptake, leading to an increase in the magnitude of Ca2+ alternans in cardiac cells, especially at fast pacing frequencies. Notably, the alternation of SR Ca2+ release precedes the alternation of SR Ca2+ load during rapid ventricular pacing.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Rizwan Qaisar, Gavin Pharaoh, Shylesh Bhaskaran, Hongyang Xu, Rojina Ranjit, Jan Bian, Bumsoo Ahn, Constantin Georgescu, Jonathan D. Wren, Holly Van Remmen
Summary: The study showed that pharmacological activation of SERCA can mitigate sarcopenia phenotype in aging mice, reversing reductions in muscle mass and force generation, and preventing an increase in mitochondrial ROS production. These effects are mediated in part by enhanced cellular energetics through activation of PGC1-alpha, UCP1, HSF1, and APMK, as well as increased regenerative capacity by suppression of MEF2C and p38 MAPK signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Weimin Yu, Gang Xu, Hui Chen, Li Xiao, Gang Liu, Pingping Hu, Siqi Li, Vivi Kasim, Chunyu Zeng, Xiaoyong Tong
Summary: Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). This study identifies the impact of C674 oxidative inactivation on pulmonary vascular remodeling and PH development, highlighting the importance of C674 in maintaining pulmonary vascular homeostasis by restricting PASMC proliferation. The IRE1 alpha/XBP1s pathway and SERCA2 may serve as potential targets for PH therapy.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biophysics
Roman Nikolaienko, Elisa Bovo, Samantha L. Yuen, Levy M. Treinen, Kaja Berg, Courtney C. Aldrich, David D. Thomas, Razvan L. Cornea, Aleksey V. Zima
Summary: Compound 1 enhances SERCA2a Ca2+-ATPase and Ca2+ transport, improves intracellular Ca2+ dynamics, and has potential therapeutic effects for heart failure.
BIOPHYSICAL JOURNAL
(2023)
Article
Oncology
Zhidong Li, Jia Guo, Yunfei Bian, Mingsheng Zhang
Summary: The study found that IMD can protect cardiomyocytes against thapsigargin-induced apoptosis, at least partially by activating the protein kinase A/SERCA pathway.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Cell Biology
Zuzana Tatarkova, Maria Bencurova, Jan Lehotsky, Peter Racay, Monika Kmetova Sivonova, Dusan Dobrota, Peter Kaplan
Summary: This study aimed to investigate how impaired Ca2+ handling in the sarcoplasmic reticulum (SR) contributes to cardiac dysfunction in hyperhomocysteinemia (HHcy). The results showed that the altered protein contents in SR Ca2+-handling proteins are associated with the impaired cardiac contractile function caused by HHcy, while oxidative damage is not involved.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Xuan Xiong, Xiaoqin Zhang, Yuan Zhang, Jiaqi Xie, Yuan Bian, Qinan Yin, Rongsheng Tong, Dongke Yu, Lingai Pan
Summary: This study found that TCEP exposure can cause cardiac fibrosis by inhibiting the expression of SERCA and leading to Ca2+ overload, which in turn triggers ER stress and overactive autophagy. The results reveal the important role of the Ca2+ overload/ER stress/autophagy axis in TCEP-induced cardiotoxicity.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Cardiac & Cardiovascular Systems
Mingke Ni, Yanhui Li, Jinhong Wei, Zhenpeng Song, Hui Wang, Jinjing Yao, Yong-Xiang Chen, Darrell Belke, John Paul Estillore, Ruiwu Wang, Alexander Vallmitjana, Raul Benitez, Leif Hove-Madsen, Wei Feng, Ju Chen, Thomas M. M. Roston, Shubhayan Sanatani, Anna Lehman, S. R. Wayne Chen
Summary: A loss-of-function RyR2-I4855M(+/-) mutation is associated with left ventricular noncompaction (LVNC), which is characterized by increased Ca2+ release and elevated end-diastolic Ca2+ levels. This mutation may contribute to the development of RyR2-associated LVNC.
CIRCULATION RESEARCH
(2023)
Article
Multidisciplinary Sciences
Fabrice Gonnot, Laura Boulogne, Camille Brun, Maya Dia, Yves Gouriou, Gabriel Bidaux, Christophe Chouabe, Claire Crola Da Silva, Sylvie Ducreux, Bruno Pillot, Andrea Kaczmarczyk, Christelle Leon, Stephanie Chanon, Coralie Perret, Franck Sciandra, Tanushri Dargar, Vincent Gache, Fadi Farhat, Laurent Sebbag, Thomas Bochaton, Helene Thibault, Michel Ovize, Melanie Paillard, Ludovic Gomez
Summary: Despite advancements in cardioprotection, novel therapeutic approaches are still required to prevent ischemia-reperfusion injury in patients. This study reveals that phosphorylation of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2) at serine 663 is a clinical and pathophysiological event affecting cardiac function. Inhibition of serine 663 phosphorylation enhances SERCA2 activity, mitigates cell death, and counteracts cytosolic and mitochondrial Ca2+ overload. These findings enhance our understanding of excitation/contraction coupling in cardiomyocytes and highlight the therapeutic potential of SERCA2 modulation in acute myocardial infarction.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Ha Thu Nguyen, Carlos Noriega Polo, Andreas Wiederkehr, Claes B. Wollheim, Kyu-Sang Park
Summary: Enhancing endoplasmic reticulum (ER) calcium uptake through activation of the sarco/endoplasmic reticulum calcium ATPase (SERCA) can improve survival and function of pancreatic ss-cells. Activation of SERCA increases insulin synthesis and exocytosis, enhances sensitivity to glucose, and improves mitochondrial bioenergetics and antioxidant capability. Targeting SERCA could be a promising therapeutic strategy for protecting ss-cells from lipotoxicity and Type 2 diabetes development.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Natthaphat Siri-Angkul, Behzad Dadfar, Riya Jaleel, Jazna Naushad, Jaseela Parambathazhath, Angelia Doye, Lai-Hua Xie, Judith Gwathmey
Summary: Heart failure remains a major issue globally, with efforts by clinicians and scientists to find effective treatments and cures not yet yielding major breakthroughs. The heart is not simply a pump, and treating heart failure requires consideration of its pathophysiological complexity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Sou Inagaki, Yoshiaki Suzuki, Keisuke Kawasaki, Rubii Kondo, Yuji Imaizumi, Hisao Yamamura
Summary: In this study, the role of mitochondrial fusion protein 2 (Mfn2) in the coupling of sarcoplasmic reticulum (SR) and mitochondria in vascular smooth muscle cells (VSMCs) was examined. It was found that Mfn2 is responsible for tethering mitochondria to SR, which regulates calcium signaling, ATP production, and cell proliferation in VSMCs.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Thirupura S. Shankar, Dinesh K. A. Ramadurai, Kira Steinhorst, Salah Sommakia, Rachit Badolia, Aspasia Thodou Krokidi, Dallen Calder, Sutip Navankasattusas, Paulina Sander, Oh Sung Kwon, Aishwarya Aravamudhan, Jing Ling, Andreas Dendorfer, Changmin Xie, Ohyun Kwon, Emily H. Y. Cheng, Kevin J. Whitehead, Thomas Gudermann, Russel S. Richardson, Frank B. Sachse, Johann Schredelseker, Kenneth W. Spitzer, Dipayan Chaudhuri, Stavros G. Drakos
Summary: The study found that VDAC2 plays a crucial role in influencing mitochondrial calcium dynamics and cellular calcium signaling. A VDAC2 agonist, efsevin, rescued the heart failure phenotype, identifying a new potential therapeutic target for heart failure.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Kazuhiro Abe, Kenta Yamamoto, Katsumasa Irie, Tomohiro Nishizawa, Atsunori Oshima
Summary: The gastric H+,K+-ATPase and Na+,K+-ATPase show differences in the number of K+ ions bound at the cation-binding site, with a mutant H+,K+-ATPase featuring two K+ ions at the site. This study provides insights into how closely-related cation pumps specify the number of K+ ions accommodated at their cation-binding sites.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Junsen Lin, Zhan Chen, Luzi Yang, Lei Liu, Peng Yue, Yueshen Sun, Mingming Zhao, Xiaoling Guo, Xiaomin Hu, Yan Zhang, Hong Zhang, Yifei Li, Yuxuan Guo, Erdan Dong
Summary: This study revealed the crucial role of SERCA2 in heart development by using gene knockout technology and demonstrated its impact on the formation of mature ventricular cardiomyocytes and gene expression. These findings provide new insights into heart development and SERCA2-based cardiac gene therapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Junwei Yu, Haining Zhang, Mingshu Zhang, Yongqiang Deng, Huiyu Wang, Jingze Lu, Tao Xu, Pingyong Xu
BIOCHEMICAL JOURNAL
(2013)
Article
Multidisciplinary Sciences
Ling Zhu, Yong-Qiang Deng, Rong-Rong Zhang, Zhen Cui, Chun-Yun Sun, Chang-Fa Fan, Xiaorui Xing, Weijin Huang, Qi Chen, Na-Na Zhang, Qing Ye, Tian-Shu Cao, Nan Wang, Lei Wang, Lei Cao, Huiyu Wang, Desheng Kong, Juan Ma, Chunxia Luo, Yanjing Zhang, Jianhui Nie, Yao Sun, Zhe Lv, Neil Shaw, Qianqian Li, Xiao-Feng Li, Junjie Hu, Liangzhi Xie, Zihe Rao, Youchun Wang, Xiangxi Wang, Cheng-Feng Qin
Summary: HB27 is a potent human monoclonal antibody that can block the binding of SARS-CoV-2 to its cellular receptor at sub-nM concentrations, as well as prevent membrane fusion. It has shown effective protection against SARS-CoV-2 in mouse models and was well tolerated in rhesus macaques. Cryo-EM studies indicate that HB27 works synergistically to prevent SARS-CoV-2 from binding to the ACE2 receptor, making it a promising candidate for immuno-therapies against COVID-19.
NATIONAL SCIENCE REVIEW
(2021)