| 15004018 |
Wang J, Wei Q, Wang CY, Hill WD, Hess DC, Dong Z: Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria. J Biol Chem. 2004 May 7;279(19):19948-54. Epub 2004 Mar 5.
Robust neuroprotective effects have been shown for minocycline. Whether it also protects nonneuronal cells or tissues is unknown. More importantly, the mechanisms of minocycline protection appear multifaceted and remain to be clarified. Here we show that minocycline can protect kidney epithelial cells in vitro and protect the kidneys from ischemic injury in vivo. We further show that Bcl-2 is a key molecular determinant of minocycline protection. Minocycline protected kidney epithelial cells against apoptosis induced by hypoxia, azide, cisplatin, and staurosporine. The protection occurred at mitochondria, involving the suppression of Bax accumulation, outer membrane damage, and cytochrome c release. Minocycline induced Bcl-2, which accumulated in mitochondria and interacted with death-promoting molecules including Bax, Bak, and Bid. Down-regulation of Bcl-2 by specific antisense oligonucleotides abolished the cytoprotective effects of minocycline. Thus, minocycline can protect neuronal as well as nonneuronal cells and tissues. One mechanism for minocycline protection involves the induction of Bcl-2, an antiapoptotic protein. |
1(0,0,0,1) |