Purchase this article with an account.
I. Kim, S.-W. Jung, M. Park, J.-I. Moon; Expression of BCL-2 Family Members Under Glutathione Depletion in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5906.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Glutathione (GSH) is known to play a critical role in the cellular defense against unregulated oxidative stress in mammalian cells including neurons. We previously demonstrated that GSH depletion induces cell death in the retina, but the mechanism of cell defense by GSH is still unclear. Thus, we here examined expression of BCL-2 family members (bcl-2, bcl-XL, bax, bak, N-BAK and bad) known to play a key role in determining cell viability.
In order to deplete intracellular GSH, we injected buthionine sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase to mice. After 0, 1, 4, and 7 days of BSO injection, total RNAs from each animals were isolated and subjected to real-time RT-RCR analysis.
Expression of bcl-XL increased one day after BSO injection, but was back to the basal level on day 4. Its expression decreased after 7 days. Expressions of bcl-2 and bax were significantly decreased from 4 days after BSO injection, whereas expression of bad was not changed. An anti-apoptotic molecule, bak displayed a significant decrease 7 days after BSO injection, whereas neuronal cell specific BAK, N-BAK was not altered in its gene expression. Taken together, we demonstrated that glutathione depletion altered expressions of BCL-2 family members in distinct manners. In particular, pro-survival molecule, bcl-2 was decreased under GSH depletion.
Thus, bcl-2 may play a critical role in GSH-dependent cellular protection in the retina against unregulated oxidative stress, and which implies bcl-2 may provide a potent therapeutic tool for cures against oxidative stress induced retinal degenerative diseases such as glaucoma, retinopathy, and age-related macular degeneration.
This PDF is available to Subscribers Only