Calcium Signaling Mediates Cell Death and Crosstalk with Autophagy in Kidney Disease

Abstract

The kidney is an important organ for the maintenance of Ca2+ homeostasis in the body. However, disruption of Ca2+ homeostasis will cause a series of kidney diseases, such as acute kidney injury (AKI), chronic kidney disease (CKD), renal ischemia/reperfusion (I/R) injury, autosomal dominant polycystic kidney disease (ADPKD), podocytopathy, and diabetic nephropathy. During the progression of kidney disease, Ca2+ signaling plays key roles in various cell activities such as necrosis, apoptosis, eryptosis and autophagy. Importantly, there are complex Ca2+ flux networks between the endoplasmic reticulum (ER), mitochondria and lysosomes which regulate intracellular Ca2+ signaling in renal cells and contribute to kidney disease. In addition, Ca2+ signaling also links the crosstalk between various cell deaths and autophagy under the stress of heavy metals or high glucose. In this regard, we present a review of Ca2+ signaling in cell death and crosstalk with autophagy and its potential as a therapeutic target for the development of new and efficient drugs against kidney diseases.

Role of PLC/IP3/IP3R axis in excess molybdenum exposure induced apoptosis in duck renal tubular epithelial cells

“…Heavy metal, ischemia, infection and poison can cause renal dysfunction and damage to renal tubular epithelial cells. 9,35 Therefore, renal tubular epithelial cells were selected as the object of the research. In the study, the data showed that excessive Mo could activate PLC/IP 3 /IP 3 R axis, which resulted in the redistribution of Ca 2+ in subcellular structure, and then caused Ca homeostasis disorder, ultimately leading to the apoptosis of duck renal tubular epithelial cells.…”

“…The renal tubule, as the main component of the basic unit of renal function, has important properties such as reabsorption, secretion and excretion, and maintaining the balance of water in the body. Heavy metal, ischemia, infection and poison can cause renal dysfunction and damage to renal tubular epithelial cells 9,35 . Therefore, renal tubular epithelial cells were selected as the object of the research.…”

Ion channels as a therapeutic target for renal fibrosis

“…In the kidney, Ca 2+ is also involved in the endocrine regulation of renal blood flow, glomerular filtration, and tubular handling of water and electrolytes. Dysregulation of Ca 2+ signaling is often thought to play an important role in the development of renal diseases such as polycystic kidney, acute kidney injury, glomerular disease, and diabetic nephropathy ( Yang and Yang, 2013 ; Ning et al, 2021 ). In addition, critical regulation of intracellular Ca 2+ levels during driving EMT is necessary for the translation of extracellular signals into gene expression effects and execution of cellular behavior.…”

Cadmium Disrupted ER Ca2+ Homeostasis by Inhibiting SERCA2 Expression and Activity to Induce Apoptosis in Renal Proximal Tubular Cells

“…Cd 2+ -disrupted intracellular calcium (Ca 2+ ) homeostasis induced autophagy inhibition, promoted oxidative stress, and thereby mediated cell apoptosis [ 4 , 5 , 6 , 7 , 8 ]. Previous studies have shown that heavy metals (Cd 2+ , Pb 2+ ) exposure induces subcellular Ca 2+ redistribution by increasing Ca 2+ release from the endoplasmic reticulum (ER) Ca 2+ stored in primary rat proximal tubular cells [ 9 , 10 , 11 ].…”