Pro‐oxidants and mitochondrial Ca²⁺: their relationship to apoptosis and oncogenesis

Abstract

Apoptosis is a physiological process for active cell removal. One of its hallmarks is an increased cytosolic Ca2+ content. Several genes involved in apoptosis control have been identified, but their mode of action is not understood in detail. Apoptosis may relate to oncogenesis, in that some malignant tumors may grow because genes engaged in apoptosis control are altered. L929 cells overexpressing the proto‐oncogen bcl‐2 have an increased mitochondrial membrane potential (δψ), as have many carcinoma cells, bcl‐2 protects L929 cells against apoptosis caused by pro‐oxidant‐induced mitochondrial Ca2+ ‘cycling’ and increased cytosolic Ca2+ levels. Nerve growth factor, which induces catalase, and inhibitors of mitochondrial Ca2+ release also prevent apoptosis. It is suggested that a pro‐oxidant‐induced Ca2+ release from mitochondria, followed by Ca2+ cycling and ATP depletion, is a common basic event during apoptosis. Accordingly, maintenance of δψ stabilizes mitochondria, thereby prevents apoptosis, and may confer increased growth potential to cells.

Down-regulation of heme oxygenase-1 by SVCV infection

“…3), which might be largely associated with production of ROS in the apoptotic process. ROS generation has been implicated in the apoptotic process and could elicit the expression of HO-1 [20,21]. Previous research showed that SVCV infection could induce apoptosis in EPC cells [22], which could result in the increase of HO-1 expression from 12 h to 24 h postinfection.…”

Oxidative stress in cells infected with bovine viral diarrhoea virus: a crucial step in the induction of apoptosis.

“…In contrast, BHA did not interact directly with BVDV, since preincubation of the virus with BHA for 1 h at 37 mC did not reduce virus infectivity (not shown). Additionally, BHT (Gogvadze et al, 1992) and cyclosporine A (CSA) (Schweizer et al, 1993) inhibit ROS-induced Ca# + -cycling in mitochondria, an important factor in ROS-induced apoptosis (Richter, 1993). However, BHT was much more toxic to BT cells than was BHA, which is also observed in hepatocytes (Thompson & Molde!…”

Calcium Homeostasis and Reactive Oxygen Species Production in Cells Transformed by Mitochondria from Individuals with Sporadic Alzheimer’s Disease

“…This delayed recovery could increase cytosolic, mitochondrial, and nuclear calcium, alter cellular excitability and signaling, and ultimately lead to apoptosis (Nicotera and Orrenius, 1992;Brini et al, 1993Brini et al, , 1994Richter, 1993;Dykens, 1994;Ghosh and Greenberg, 1995;Oshimi and Miyazaki, 1995;Khan et al, 1996;Simpson and Russell, 1996;Tong et al, 1996).…”