Keywords
Calcium signaling
Liver diseases
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Abstract
Aims: To investigate the relationship between calcium (Ca2+) signaling and reactive oxygen species (ROS) in the development of liver diseases, focusing on molecular mechanisms and their implications for liver health. Literature review: Oxidative stress, caused by the accumulation of free radicals, results in significant cellular damage, especially when endogenous antioxidants are insufficient. Ca2+ signaling is vital for liver functions, such as biliary cartilage and glucose metabolism, and is regulated by specific receptors in the endoplasmic reticulum (ER). A failure in communication between the ER and mitochondria, crucial for cellular homeostasis, can lead to liver disease. Proteins such as Ca2+ channels and receptors modulate this interaction, and their dysfunction can alter mitochondrial Ca2+ concentrations, increasing cellular damage. Furthermore, ER stress and ROS production are associated with hepatic stimulation. Dysfunction in Ca2+ signaling is also linked to liver cancer progression. Final considerations: Disturbances in Ca2+ signaling and increased ROS are closely linked to the development of several liver diseases, including steatosis, NAFLD, cirrhosis and cancer. Understanding these mechanisms is crucial for improving liver health and developing new therapeutic approaches.
References
AJOOLABADY A, et al. Endoplasmic reticulum stress in liver diseases. Hepatology, 2023; 77(2): 619-639.
ALI ES, et al. Deranged hepatocyte intracellular Ca2+ homeostasis and the progression of non-alcoholic fatty liver disease to hepatocellular carcinoma. Cell Calcium, 2019; 82: 102057.
AMAYA MJ e NATHANSON MH. Calcium signaling in the liver. Compr Physiol., 2013; 1: 515-39.
BEAULANT A, et al. Endoplasmic reticulum-mitochondria miscommunication is an early and causal trigger of hepatic insulin resistance and steatosis. J Hepatol., 2022; 77(3): 710-722.
CHEN CC, et al. Emerging Roles of Calcium Signaling in the Development of Non-Alcoholic Fatty Liver Disease. Int J Mol Sci., 2021; 23(1): 256.
DEJOS C, et al. The Two-Way Relationship Between Calcium and Metabolism in Cancer. Front Cell Dev Biol., 2020; 13: 573747.
FERIOD CN, et al. Hepatic Inositol 1,4,5 Trisphosphate Receptor Type 1 Mediates Fatty Liver. Hepatol Commun., 2017; 1(1): 23-35.
FRANÇA A, et al. Effects of Endotoxin on Type 3 Inositol 1,4,5-Trisphosphate Receptor in Human Cholangiocytes. Hepatology, 2019; 69: 817–830.
GUERRA MT, et al. Expression of the type 3 InsP3 receptor is a final common event in the development of hepatocellular carcinoma. Gut, 2019; 68(9): 1676-1687.
HUANG Z, et al. Downregulation of calbindin 1, a calcium-binding protein, reduces the proliferation of osteosarcoma cells. Oncol Lett., 2017; 13(5): 3727-3733.
JIN C, et al. Calcium transfer between endoplasmic reticulum and mitochondria in liver diseases. FEBS Lett., 2021; 595(10): 1411-1421.
KHAMPHAYA T, et al. Nonalcoholic fatty liver disease impairs expression of the type II inositol 1,4,5-trisphosphate receptor. Hepatology, 2018; 67(2): 560-574.
LEBEAUPIN C, et al. Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. J Hepatol., 2018; 69(4): 927-947.
LEMOS FO, et al. Inositol 1,4,5-trisphosphate receptor in the liver: Expression and function. World J Gastroenterol., 2019; 25(44): 6483-6494.
LIANG JQ, et al. Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling. Nat Commun. 2018; 9(1): 4490.
LY LD, et al. Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes. Exp Mol Med. 2017; 49(2): e291.
MILLANA FE, et al. On the mechanism of calcium-dependent activation of NADPH oxidase 5 (NOX5). FEBS J., 2020; 287: 2486-2503.
OLIVA-VILARNAU NH, et al. Calcium Signaling in Liver Injury and Regeneration. Frontiers in Medicine, 2018; 5.
RODRIGUES MA, et al. Calcium Signaling in Cholangiocytes: Methods, Mechanisms, and Effects. Int J Mol Sci., 2018; 19(12): 3913.
URESHINO RP, et al. Calcium signaling alterations, oxidative stress, and autophagy in aging. Antioxid Redox Signal., 2014; 21(1): 123-37.
WANG J, et al. Mutual interaction between endoplasmic reticulum and mitochondria in nonalcoholic fatty liver disease. Lipids Health Dis., 2020; 19(1): 72.
WANG W, et al. Mitofusin-2 triggers mitochondria Ca2+ influx from the endoplasmic reticulum to induce apoptosis in hepatocellular carcinoma cells. Cancer Lett., 2015; 358(1): 47-58.
YUAN Y, et al. Cross-talk between calcium and reactive oxygen species signaling. Acta Pharmacologica Sinica, 2006; 27: 821–826.