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Mitochondrial Dysfunction and Ca 2+ Overload Contributes to Hesperidin Induced Paraptosis in Hepatoblastoma Cells, HepG2
Author(s) -
Yumnam Silvia,
Hong Gyeong Eun,
Raha Suchismita,
Saralamma Venu Venkatarame Gowda,
Lee Ho Jeong,
Lee WonSup,
Kim EunHee,
Kim Gon Sup
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25222
Subject(s) - ryanodine receptor , mitochondrion , ruthenium red , uniporter , endoplasmic reticulum , apoptosis , hesperidin , chemistry , microbiology and biotechnology , programmed cell death , biochemistry , biology , calcium , cytosol , medicine , enzyme , alternative medicine , organic chemistry , pathology
Paraptosis is a programmed cell death which is morphologically and biochemically different from apoptosis. In this study, we have investigated the role of Ca 2+ in hesperidin‐induced paraptotic cell death in HepG2 cells. Increase in mitochondrial Ca 2+ level was observed in hesperidin treated HepG2 cells but not in normal liver cancer cells. Inhibition of inositol‐1,4,5‐triphosphate receptor (IP 3 R) and ryanodine receptor also block the mitochondrial Ca 2+ accumulation suggesting that the release of Ca 2+ from the endoplasmic reticulum (ER) may probably lead to the increase in mitochondrial Ca 2+ level. Pretreatment with ruthenium red (RuRed), a Ca 2+ uniporter inhibitor inhibited the hesperidin‐induced mitochondrial Ca 2+ overload, swelling of mitochondria, and cell death in HepG2 cells. It has also been demonstrated that mitochondrial Ca 2+ influxes act upstream of ROS and mitochondrial superoxide production. The increased ROS production further leads to mitochondrial membrane loss in hesperidin treated HepG2 cells. Taken together our results show that IP 3 R and ryanodine receptor mediated release of Ca 2+ from the ER and its subsequent influx through the uniporter into mitochondria contributes to hesperidin‐induced paraptosis in HepG2 cells. J. Cell. Physiol. 231: 1261–1268, 2016. © 2015 Wiley Periodicals, Inc.