Hypocalcemia in sepsis: analysis of the subcellular distribution of Ca2+ in septic rats and LPS/TNF-α-treated HUVECs

  • Wencheng He 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
  • Lei Huang 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
  • Hua Luo 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
  • Yang Zang 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
  • Youzhong An Department of Intensive Care Unit, Peking University People’s Hospital, Beijing, 100044, China
  • Weixing Zhang 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
Keywords: Sepsis, Hypocalcemia, Calcium overload, Subcellular Redistribution, Mechanism

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.

Published
2020-08-31
How to Cite
1.
He W, Huang L, Luo H, Zang Y, An Y, Zhang W (2020) Hypocalcemia in sepsis: analysis of the subcellular distribution of Ca2+ in septic rats and LPS/TNF-α-treated HUVECs. J Infect Dev Ctries 14:908-917. doi: 10.3855/jidc.12341
Section
Original Articles