Inhibition of store-operated Ca2+ channels prevent ethanol-induced intracellular Ca2+ increase and cell injury in a human hepatoma cell line

The effect of oleuropein from olive leaf (Olea europaea) extract on Ca2+ homeostasis, cytotoxicity, cell cycle distribution and ROS signaling in HepG2 human hepatoma cells

“…The results suggest that oleuropein induced Ca 2þ entry through 2-APB or SKF96365-sensitive store-operated Ca 2þ channels because two store-operated Ca 2þ channel blockers in liver cells, 2-APB (Liu et al, 2012) and SKF96365 (Fagan and Romani, 2001), significantly inhibited oleuropein-induced [Ca 2þ ] i rises by approximately half in Ca 2þ -containing medium, which is also similar to the magnitude of oleuropein-induced Ca 2þ influx. Previous studies showed that inhibition of store-operated Ca 2þ channels by 2-APB suppressed ethanol-or gypenosides-induced [Ca 2þ ] i rises in HepG2 cells (Liu et al, 2012;Sun et al, 2013). In addition, the store-operated Ca 2þ channel inhibitor SKF96365 also inhibited ATP-induced [Ca 2þ ] i rises in HepG2 cells (Xie et al, 2014).…”

“…Because oleuropein did not induce [Ca 2þ ] i rises in AML12 cells, HA22T and HA59T cells, this study focused on the underlying mechanism of oleuropein-induced [Ca 2þ ] i rises in HepG2 cells. It has been shown that store-operated Ca 2þ channels (Liu et al, 2012) contribute to Ca 2þ entry in HepG2 cells. However, the role of these channels in oleuropein-induced Ca 2þ entry in HepG2 cells is unclear.…”

“…Fig. 3A shows that two store-operated Ca 2þ channel blockers: 2-APB (20 mM) (Liu et al, 2012) and SKF96365 (5 mM) (Fagan and Romani, 2001) were applied 1 min before 150 mM oleuropein in Ca 2þ -containing medium. Addition of 2-APB or SKF96365 alone did not alter baseline [Ca 2þ ] i (data not shown).…”

STIM and Orai proteins as novel targets for cancer therapy. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis

“…Interestingly, STIM1 was discovered as a tumor suppressor gene in skeletal muscle tumors years before its Ca 2ϩ handling role was established (86). Further, a role for STIM and Orai proteins is also emerging in ovarian (89), nasopharyngeal (121), hepatocellular (62,112,114), and renal carcinomas (49). Collectively, a large body of data has established a critical role for STIMs and Orais in mediating tumorigenesis (for summary, please refer to Table 1 and Fig.…”

Role of mitochondrial damage in Cr(VI)‑induced endoplasmic reticulum stress in L‑02 hepatocytes

“…The production of mitochondrial ROS, including oxygen free radicals, such as superoxide anion radicals (O 2˙-) and hydroxyl radicals (˙OH), and non-radical oxidants, such as singlet oxygen ( 1 O 2 ) and hydrogen peroxide (H 2 O 2 ), is involved in the pathogenesis of various diseases and disorders, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis; this is due to its harmful effects on proteins, lipids and DNA that may cause cell damage and even death (6). A previous study demonstrated that mitochondrial respiratory chain complex (MRCC) I (NADH-ubiquinone oxidoreductase) was the principal source of ROS as a consequence of electron leakage during respiration in mitochondria under pathological conditions; however, not under resting and healthy conditions; therefore, it is not unexpected that >40% of all mitochondrial-associated disorders are associated with mutations in subunits of MRCC I (7). MRCC III [cytochrome c (Cyt C) reductase] is additionally considered to be the primary site on the electron transfer chain to generate ROS (8); however, there remains a lack of exact mechanistic knowledge of the architecture of mitochondrial ROS-generation systems, including MRCC I and III, and of detailed insights into the molecular mechanisms controlling their expression or activities.…”