Wencheng He1, Lei Huang2, Hua Luo3, Yang Zang4, Youzhong An5, Weixing Zhang6. 1. Department of Intensive Care Unit, Peking University Shenzhen Hospital, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, No.1120, Lianhua Road, Futian District, Shenzhen, 518000, China. hewenchengsg@163.com. 2. Department of Intensive Care Unit, Peking University Shenzhen Hospital, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, No.1120, Lianhua Road, Futian District, Shenzhen, 518000, China. hl0248@outlook.com. 3. Department of Intensive Care Unit, Peking University Shenzhen Hospital, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, No.1120, Lianhua Road, Futian District, Shenzhen, 518000, China. luoxiaoer@hotmail.com. 4. Department of Intensive Care Unit, Peking University Shenzhen Hospital, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, No.1120, Lianhua Road, Futian District, Shenzhen, 518000, China. 1967160326@qq.com. 5. Department of Intensive Care Unit, Peking University People's Hospital, Beijing, 100044, China. youbjicu@163.com. 6. Department of Intensive Care Unit, Peking University Shenzhen Hospital, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, No.1120, Lianhua Road, Futian District, Shenzhen, 518000, China. zhangwx@hotmail.com.
Abstract
INTRODUCTION: Hypocalcemia has been widely recognized in sepsis patients. However, the cause of hypocalcemia in sepsis is still not clear, and little is known about the subcellular distribution of Ca2+ in tissues during sepsis. METHODOLOGY: We measured the dynamic change in Ca2+ levels in body fluid and subcellular compartments, including the cytosol, endoplasmic reticulum and mitochondria, in major organs of cecal ligation and puncture (CLP)-operated rats, as well as the subcellular Ca2+ flux in HUVECs which treated by endotoxin and cytokines. RESULTS: In the model of CLP-induced sepsis, the blood and urinary Ca2+ concentrations decreased rapidly, while the Ca2+ concentration in ascites fluid increased. The Ca2+ concentrations in the cytosol, ER, and mitochondria were elevated nearly synchronously in major organs in our sepsis model. Moreover, the calcium overload in CLP-operated rats treated with calcium supplementation was more severe than that in the non-calcium-supplemented rats but was alleviated by treatment with the calcium channel blocker verapamil. Similar subcellular Ca2+ flux was found in vitro in HUVECs and was triggered by lipopolysaccharide (LPS)/TNF-α. CONCLUSIONS: Ca2+ influx from the blood into the intercellular space and Ca2+ release into ascites fluid may cause hypocalcemia in sepsis and that this process may be due to the synergistic effect of endotoxin and cytokines. Copyright (c) 2020 Wencheng He, Lei Huang, Hua Luo, Yang Zang, Youzhong An, Weixing Zhang.
INTRODUCTION:Hypocalcemia has been widely recognized in sepsispatients. However, the cause of hypocalcemia in sepsis is still not clear, and little is known about the subcellular distribution of Ca2+ in tissues during sepsis. METHODOLOGY: We measured the dynamic change in Ca2+ levels in body fluid and subcellular compartments, including the cytosol, endoplasmic reticulum and mitochondria, in major organs of cecal ligation and puncture (CLP)-operated rats, as well as the subcellular Ca2+ flux in HUVECs which treated by endotoxin and cytokines. RESULTS: In the model of CLP-induced sepsis, the blood and urinary Ca2+ concentrations decreased rapidly, while the Ca2+ concentration in ascites fluid increased. The Ca2+ concentrations in the cytosol, ER, and mitochondria were elevated nearly synchronously in major organs in our sepsis model. Moreover, the calcium overload in CLP-operated rats treated with calcium supplementation was more severe than that in the non-calcium-supplemented rats but was alleviated by treatment with the calcium channel blocker verapamil. Similar subcellular Ca2+ flux was found in vitro in HUVECs and was triggered by lipopolysaccharide (LPS)/TNF-α. CONCLUSIONS:Ca2+ influx from the blood into the intercellular space and Ca2+ release into ascites fluid may cause hypocalcemia in sepsis and that this process may be due to the synergistic effect of endotoxin and cytokines. Copyright (c) 2020 Wencheng He, Lei Huang, Hua Luo, Yang Zang, Youzhong An, Weixing Zhang.
Authors: Bruna A C Rattis; Ana C Freitas; Jordana F Oliveira; João L A Calandrini-Lima; Maria J Figueiredo; Danilo F Soave; Simone G Ramos; Mara R N Celes Journal: Oxid Med Cell Longev Date: 2021-04-08 Impact factor: 6.543