Reactive oxygen species produced by NADPH oxidase, xanthine oxidase, and mitochondrial electron transport system mediate heat shock-induced MMP-1 and MMP-9 expression.
In addition to ultraviolet radiation, human skin is also exposed to infrared radiation (IR) from natural sunlight. IR typically increases the skin temperature. This study examined whether or not heat shock-induced ROS stimulates MMPs in keratinocyte HaCaT cells. In HaCaT cells, heat shock was found to increase the intracellular ROS levels, including hydrogen peroxide and superoxide. The heat shock treatment induced MMP-1 and MMP-9, but not MMP-2, at the mRNA and protein levels. Moreover, heat shock caused the rapid activation of the three distinct MAPKs, ERK, JNK, and p38 kinase. The heat shock-induced expression of MMP-1 and MMP-9 was significantly suppressed by a pretreatment with the antioxidant NAC or catalase. On the other hand, SOD inhibited heat shock-induced activity of MMP-9 induction, but not MMP-1. A pretreatment with NAC or catalase, but not SOD, attenuated the phosphorylation of ERK, JNK, and p38 kinase by heat shock. The potential sites of ROS generation by heat shock along with its role in the heat shock-induced expression of MMP-1 and MMP-9 were next analyzed. These results indicate that heat shock-induced ROS is promoted via NADPH oxidase, xanthine oxidase, and mitochondria. Indeed, the NADPH oxidase and xanthine oxidase activities were increased by heat shock. Overall, the ROS produced by heat shock may play an important role in the heat shock-induced activation of MAPKs, which can induce MMP-1 and-9 expressions.
Department of Dermatology, Seoul National University College of Medicine, Seoul National University, Seoul, Korea.
Mi Hee
MH
Shin
Young Ji
YJ
Moon
Jo-Eun
JE
Seo
Youngae
Y
Lee
Kyu Han
KH
Kim
Jin Ho
JH
Chung
D000111:Acetylcysteine / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D004579:Electron Transport; D006358:Hot Temperature; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D019255:NADPH Oxidases / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000502:physiology*
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013481:Superoxides; D002374:Catalase; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D000111:Acetylcysteine