Shin Mi Hee, Moon Young Ji, Seo Jo-Eun, Lee Youngae, Kim Kyu Han, Chung Jin Ho
Department of Dermatology, Seoul National University College of Medicine, Seoul National University, Seoul, Korea.
Free Radic Biol Med. 2008 Feb 15;44(4):635-45. doi: 10.1016/j.freeradbiomed.2007.10.053. Epub 2007 Nov 12.
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.
除了紫外线辐射外，人类皮肤还会受到来自自然阳光的红外线辐射（IR）。红外线通常会使皮肤温度升高。本研究检测了热休克诱导的活性氧（ROS）是否会刺激角质形成细胞HaCaT中的基质金属蛋白酶（MMPs）。在HaCaT细胞中，发现热休克会增加细胞内ROS水平，包括过氧化氢和超氧化物。热休克处理在mRNA和蛋白质水平上诱导了MMP-1和MMP-9，但未诱导MMP-2。此外，热休克导致三种不同的丝裂原活化蛋白激酶（MAPKs），即细胞外信号调节激酶（ERK）、c-Jun氨基末端激酶（JNK）和p38激酶迅速激活。用抗氧化剂N-乙酰半胱氨酸（NAC）或过氧化氢酶预处理可显著抑制热休克诱导的MMP-1和MMP-9表达。另一方面，超氧化物歧化酶（SOD）抑制热休克诱导的MMP-9活性，但不抑制MMP-1。用NAC或过氧化氢酶预处理，而不是SOD，可减弱热休克引起的ERK、JNK和p38激酶的磷酸化。接下来分析了热休克产生ROS的潜在位点及其在热休克诱导的MMP-1和MMP-9表达中的作用。这些结果表明，热休克诱导的ROS通过NADPH氧化酶、黄嘌呤氧化酶和线粒体产生。事实上，热休克会增加NADPH氧化酶和黄嘌呤氧化酶的活性。总体而言，热休克产生的ROS可能在热休克诱导的MAPKs激活中起重要作用，而MAPKs激活可诱导MMP-1和MMP-9表达。
