Minocycline Up-regulates Bcl-2 and Protects against Cell Death in Mitochondria

Jinzhao Wang, QingQing Wei, Cong Yi Wang, William D Hill, David C Hess, Zheng Dong

Research output: Contribution to journalArticle

215 Citations (Scopus)

Abstract

Robust neuroprotective effects have been shown for minocycline. Whether it also protects nonneuronal cells or tissues is unknown. More importantly, the mechanisms of minocylcine 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.

Original languageEnglish (US)
Pages (from-to)19948-19954
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number19
DOIs
StatePublished - May 7 2004

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Minocycline
Mitochondria
Cell death
Cell Death
Up-Regulation
Kidney
Epithelial Cells
Tissue
Staurosporine
Azides
Antisense Oligonucleotides
Neuroprotective Agents
Cytochromes c
Cisplatin
Down-Regulation
Apoptosis
Membranes
Molecules
Wounds and Injuries

ASJC Scopus subject areas

  • Biochemistry

Cite this

Minocycline Up-regulates Bcl-2 and Protects against Cell Death in Mitochondria. / Wang, Jinzhao; Wei, QingQing; Wang, Cong Yi; Hill, William D; Hess, David C; Dong, Zheng.

In: Journal of Biological Chemistry, Vol. 279, No. 19, 07.05.2004, p. 19948-19954.

Research output: Contribution to journalArticle

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AU - Dong, Zheng

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