Minocycline inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after treatment with kainic acid in mice

Heo, Kyoung; Cho, Yang-Je; Cho, Kyoungjoo; Kim, Hyun Woo; Kim, Hyun-Jung; Shin, Ha Young; Lee, Ki Young; Kim, Gyung Whan

doi:10.1016/j.neulet.2006.01.027

Cited by 82 publications

(49 citation statements)

References 18 publications

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“…Also, minocycline inhibits JNK1/2 and ERK1/2 activation and exerts antiinflammatory properties in the central nervous system (33). Moreover, minocycline inhibits both caspase-dependent and -independent apoptotic pathways and possesses neuroprotective effects against hippocampal damage (34,35). We hypothesized that minocycline can inhibit H 2 O 2 -induced p38 and JNK activation and exert protective effects on melanocytes.…”

Section: Discussionmentioning

confidence: 99%

Minocycline protects melanocytes against H2O2-inducedcell death via JNK and p38 MAPK pathways

Song

Xu²,

Pan³

et al. 2008

Int J Mol Med

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Abstract.Vitiligo is an acquired and progressive disorder manifested by the selective destruction of melanocytes in the skin. An extremely high level of hydrogen peroxide (H 2 O 2 ) in plasma as well as in lesional skin has been reported in vitiligo patients. High H 2 O 2 level has been suggested to be responsible for the disappearance of melanocytes in vitiligo. JNK and p38 MAPK are strongly induced by oxidative stress and related to neuron loss in neurodegenerative disorders. Minocycline, an antibiotic possessing antioxidant activity, is capable of attenuating oxidative stress-induced neurotoxicity. To investigate whether minocycline rescues melanocytes from H 2 O 2 -induced apoptosis, cultured mouse melanocytes (B10BR) were treated with H 2 O 2 in the presence or absence of minocycline. Our data showed that H 2 O 2 decreases cell viability in a concentration-dependent manner which is attenuated by minocycline. Also, H 2 O 2 treatment activates JNK and p38 MAPK, and executive caspase 3 in B10BR cells. Minocycline significantly inhibits H 2 O 2 -induced activation of JNK, p38 MAPK and caspase 3. Collectively, we concluded that minocycline protects melanocytes against H2O2-induced apoptosis in vitro. Its protective effect is associated with the inhibition of JNK and p38 MAPK. Our findings suggest that minocycline, a clinically well-tolerated, safe antibiotic, may be used to prevent melanocyte loss in the early stage of vitiligo.

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Section: Discussionmentioning

confidence: 99%

Minocycline protects melanocytes against H2O2-inducedcell death via JNK and p38 MAPK pathways

Song

Xu²,

Pan³

et al. 2008

Int J Mol Med

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“…Nuclear translocation of AIF has been reported following seizures (Heo et al, 2006;Wang et al, 2008), and endoG heterozygous mice had less kainic acid (KA) SE-induced neuronal death in hippocampus (Wu et al, 2004). In the latter instance, however, the endoG heterozygous mice were 129/Sv crossed with C57BL/6; the latter are resistant to KASE-induced neuronal death (Schauwecker and Steward, 1997), so this complicates interpretation of the protective effect of the hetereozygotes.…”

Section: Translocation Of Mitochondrial Proteinsmentioning

confidence: 99%

Nuclear translocation of mitochondrial cytochrome c, lysosomal cathepsins B and D, and three other death‐promoting proteins within the first 60 minutes of generalized seizures

Zhao

Aviles

Fujikawa

2010

J of Neuroscience Research

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We have shown that generalized seizures produce necrotic neurons with caspase-independent nuclear pyknosis and DNA fragmentation. In this study, we determined the time course of translocation of mitochondrial cytochrome c, apoptosis-inducing factor, endonuclease G, lysosomal cathepsins B and D, and DNase II with respect to signs of irreversible neuronal damage. Adult male Wistar rats underwent lithium-pilocarpine-induced seizures lasting for 60 min, 3 hr, and 3 hr with 6- or 24-hr survival periods, after which the brains were prepared for immunofluorescence microscopic examination of piriform cortex. Contrary to expectation, cytochrome c and cathepsins B and D translocated to neuronal nuclei with DNase II, endonuclease G, and apoptosis-inducing factor within 60 min of seizure onset and persisted for 24 hr after 3-hr seizures. After 60-min seizures, some neurons showed translocation of the death-promoting proteins in normal-appearing neurons, prior to their appearance in irreversibly damaged neurons. Western blots of subcellular fractions of cytochrome c and cathepsins B and D confirmed their nuclear translocation. This is the first evidence of nuclear translocation of cathepsins B and D and the first in vivo evidence of nuclear translocation of cytochrome c. The appearance of these mitochondrial proteins and lysosomal enzymes before signs of irreversible neuronal death suggests that they could contribute to seizure-induced nuclear pyknosis and DNA fragmentation.

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“…In addition to its antibiotic properties, minocycline has been reported to have neuroprotective effects in various experimental models of cerebral ischemia (Yrjanheikki et al, 1999), traumatic brain injury (Sanchez Mejia et al, 2001), amyotrophic lateral sclerosis (ALS) (Zhu et al, 2002), Parkinson's diseases (PD) (Wu et al, 2002), kainic acid treatment (Heo et al, 2006), Huntington's disease (HD) (Chen et al, 2000;Wang et al, 2003), and multiple sclerosis (Popovic et al, 2002). Additionally, minocycline was reported to attenuate white matter damage in a rat model of chronic cerebral hypoperfusion .…”

Section: Introductionmentioning

confidence: 99%

Minocycline Attenuates Neuronal Cell Death and Improves Cognitive Impairment in Alzheimer's Disease Models

Choi

Kim

Shin

et al. 2007

Neuropsychopharmacol

259

179

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Minocycline is a semi-synthetic tetracycline antibiotic that effectively crosses the blood-brain barrier. Minocycline has been reported to have significant neuroprotective effects in models of cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, and Huntington's and Parkinson's diseases. In this study, we demonstrate that minocycline has neuroprotective effects in in vitro and in vivo Alzheimer's disease models. Minocycline was found to attenuate the increases in the phosphorylation of double-stranded RNAdependent serine/threonine protein kinase, eukaryotic translation initiation factor-2 a and caspase 12 activation induced by amyloid b peptide 1-42 treatment in NGF-differentiated PC 12 cells. In addition, increases in the phosphorylation of eukaryotic translation initiation factor-2 a were attenuated by administration of minocycline in Tg2576 mice, which harbor mutated human APP695 gene including the Swedish double mutation and amyloid b peptide 1-42 -infused rats. We found that minocycline administration attenuated deficits in learning and memory in amyloid b peptide 1-42 -infused rats. Increased phosphorylated state of eukaryotic translation initiation factor-2 a is observed in Alzheimer's disease patients' brains and may result in impairment of cognitive functions in Alzheimer's disease patients by decreasing the efficacy of de novo protein synthesis required for synaptic plasticity. On the basis of these results, minocycline may prove to be a good candidate as an effective therapeutic agent for Alzheimer's disease.

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Minocycline inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after treatment with kainic acid in mice

Cited by 82 publications

References 18 publications

Minocycline protects melanocytes against H2O2-inducedcell death via JNK and p38 MAPK pathways

Minocycline protects melanocytes against H2O2-inducedcell death via JNK and p38 MAPK pathways

Nuclear translocation of mitochondrial cytochrome c, lysosomal cathepsins B and D, and three other death‐promoting proteins within the first 60 minutes of generalized seizures

Minocycline Attenuates Neuronal Cell Death and Improves Cognitive Impairment in Alzheimer's Disease Models

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