Minocycline protects melanocytes against H2O2-induced cell death via JNK and p38 MAPK pathways.
Vitiligo is an acquired and progressive disorder manifested by the selective destruction of melanocytes in the skin. An extremely high level of hydrogen peroxide (H2O2) in plasma as well as in lesional skin has been reported in vitiligo patients. High H2O2 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 H2O2-induced apoptosis, cultured mouse melanocytes (B10BR) were treated with H2O2 in the presence or absence of minocycline. Our data showed that H2O2 decreases cell viability in a concentration-dependent manner which is attenuated by minocycline. Also, H2O2 treatment activates JNK and p38 MAPK, and executive caspase 3 in B10BR cells. Minocycline significantly inhibits H2O2-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.
Song
Xiuzu
X
Department of Dermatology, the Third Hospital of Hangzhou, Hangzhou, PR China.
Xu
Aie
A
Pan
Wei
W
Wallin
Brittany
B
Kivlin
Rebecca
R
Lu
Shan
S
Cao
Cong
C
Bi
Zhigang
Z
Wan
Yinsheng
Y
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008911:Minocycline / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
D008543:Melanins; D011518:Proto-Oncogene Proteins; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human; D053148:Caspase 3; D008911:Minocycline