Is Hydrogen Peroxide a Suitable Apoptosis Inducer for All Cell Types?

Abstract

Hydrogen peroxide is currently the most widely used apoptosis inducer due to its broad cytotoxic efficacy against nearly all cell types. However, equivalent cytotoxicity is achieved over a wide range of doses, although the reasons for this differential sensitivity are not always clear. In this study, three kinds of cells, the 293T cell line, primary fibroblasts, and terminally differentiated myocardial cells, were treated with a wide range of H2O2 doses. Times to apoptosis initiation and end were measured cytochemically and the changes in expression of caspase-9, P53, NF-κB, and RIP were determined by RT-PCR. The 293T cell line was the most sensitive to H2O2, undergoing necroptosis and/or apoptosis at all concentrations from 0.1 to 1.6 mM. At > 0.4 mM, H2O2 also caused necroptosis in primary cells. At < 0.4 mM, however, primary cells exhibited classic signs of apoptosis, although they tended to survive for 36 hours in < 0.2 mM H2O2. Thus, H2O2 is a broadly effective apoptosis inducer, but the dose range differs by cell type. For cell lines, a low dose is required and the exposure time must be reduced compared to primary cells to avoid cell death primarily by necroptosis or necrosis.

Neuronal‐like differentiated SH‐SY5Y cells adaptation to a mild and transient H2O2‐induced oxidative stress

“…In this context, the discrepancy between results from differentiated neuronal cells and those obtained in other cell types may be explained by this clue and, in addition, by the different range of H 2 O 2 concentration applied to induce lysis/apoptosis. In particular, the evidence that cell survival for 36 hours in H 2 O 2 at concentrations lower than 0.2mM and, moreover, 24‐hour exposure to 100μM H 2 O 2 not leading to SH‐SY5H neuroblastoma cells apoptosis are not in line with what is presently proven in neuronal‐like differentiated SH‐SY5H cells.…”

“…Hydrogen peroxide-induced oxidative stress generating ROS may act by causing neuronal death or, indirectly, by provoking apoptosis. 26,27 Nonetheless, a mild and transient exposure to The purpose of the present study was to verify whether neuronallike differentiated SH-SY5Y cells may adapt to a mild and transient H 2 O 2 -induced oxidative stress, giving rise to PC response 9 for counteracting detrimental effects of oxidant stressors. It is already known that H 2 O 2 may display a variety of effects according to both cell target and its range of concentration.…”

“…Hydrogen peroxide–induced oxidative stress generating ROS may act by causing neuronal death or, indirectly, by provoking apoptosis . Nonetheless, a mild and transient exposure to H 2 O 2 here represented by 24‐hour exposure to 10μM H 2 O 2 , which means a mild and transient presence of free radicals, can elicit a protective effect providing neurons with more resistance to subsequent oxidative challenges.…”

“…The purpose of the present study was to verify whether neuronal‐like differentiated SH‐SY5Y cells may adapt to a mild and transient H 2 O 2 ‐induced oxidative stress, giving rise to PC response for counteracting detrimental effects of oxidant stressors. It is already known that H 2 O 2 may display a variety of effects according to both cell target and its range of concentration . Therefore, the first goal was to select lytic concentrations to induce damage as well as not lytic concentrations to stimulate PC response.…”

“…Moreover, high expression levels of Bcl‐2 have been reported to last longer than 24 hours after pre‐exposure to H 2 O 2 in preconditioned rat cardiomyocytes, in line with the range of time used in the present PC protocol. Xiang et al reported about cell susceptibility to H 2 O 2 ‐induced apoptosis (0.1mM‐1.6mM range), proving that cell response to this oxidant cannot be univocally described, depending on cell type, proliferation, cell density, and stage of differentiation and giving rise to the question whether or not H 2 O 2 has a selectivity in different cell lines. In this context, the discrepancy between results from differentiated neuronal cells and those obtained in other cell types may be explained by this clue and, in addition, by the different range of H 2 O 2 concentration applied to induce lysis/apoptosis.…”