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

Abstract

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.

The role of VIT1/FBXO11 in the regulation of apoptosis and tyrosinase export from endoplasmic reticulum in cultured melanocytes

“…Epidermis was separated from the dermis and epidermal cells were suspended and cultured in Ham's F10 nutrient medium with 10% fetal bovine serum, 85 nM 12-O-tetradecanoylphorbol-13-acetate (TPA), 0.1 mM 3-isobutyl-1-methylxanthine (IBMX), 2.5 nM cholera toxin (CT), and 100 μg/ml geneticin. B10BR mouse melanocytes were cultured in Ham's F12 supplemented with 10% horse serum, 50 ng/ml phorbol 12-myristate 13-acetate (TPA) and 1% penicillin/ streptomycin (9,10). All cells were grown at 37˚C with 5% CO 2 .…”

Analysis of changes in microRNA expression profiles in response to the troxerutin-mediated antioxidant effect in human dermal papilla cells

“…KEGG pathway analysis of the target genes of the upregulated and downregulated miRNAs revealed 18 and 23 pathways, respectively, were statistically enriched. Among these, the WNT and MAPK signaling pathways, which were the most markedly enriched pathways associated with the target genes of the upregulated and downregulated miRNAs, are involved in the regulation of H 2 O 2 -mediated cellular stress, including apoptosis and antioxidative mechanisms (41)(42)(43)(44)(45), suggesting that the miRNAs altered by troxerutin may be involved in protective mechanisms against H 2 O 2 -induced damage through the regulation of these pathways.…”

Activation of Type 4 Metabotropic Glutamate Receptor Attenuates Oxidative Stress-Induced Death of Neural Stem Cells with Inhibition of JNK and p38 MAPK Signaling

“…Links between JNK/p38 phosphorylation and cell death upon oxidative stress are well characterized in various types of cells, including neural cells [23,[54][55][56][57]. During experimental oxidative stress-induced cell apoptosis, JNK and p38 were phosphorylated by H 2 O 2 stimulation and caspase cascades in suffered cells were consequently activated, which resulted in cell death [41,[58][59][60], and inhibition of JNK and p38 phosphorylation may play a role in protecting cells against oxidative injuries [22,41,43,54]. We cannot identify if there is crosstalking between the two signal pathways, which may play the synergistic or antistatic roles with each other in oxidative injuries of NSCs.…”