Hydroxyl radical mediates cisplatin-induced apoptosis in human hair follicle dermal papilla cells and keratinocytes through Bcl-2-dependent mechanism.
Hydroxyl radical mediates cisplatin-induced apoptosis in human hair follicle dermal papilla cells and keratinocytes through Bcl-2-dependent mechanism.
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DOI：
10.1007/s10495-011-0609-x
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发表时间：
2011-08
期刊：
影响因子：
7.2
通讯作者：
Rojanasakul, Yon
中科院分区：
文献类型：
--
作者：
Luanpitpong, Sudjit;Nimmannit, Ubonthip;Chanvorachote, Pithi;Leonard, Stephen S.;Pongrakhananon, Varisa;Wang, Liying;Rojanasakul, Yon
化疗诱导毛囊细胞大量凋亡与化疗诱导性脱发（CIA）的发病机制有关，但其调控机制尚不清楚。本研究研究了顺铂对人毛囊真皮乳头细胞和HaCaT角质形成细胞的凋亡作用，并确定了参与该过程的特异性活性氧（ROS）的身份和作用。顺铂处理细胞诱导ROS生成，caspase激活和凋亡细胞死亡平行增加。抗氧化剂抑制ROS生成抑制顺铂的凋亡作用，提示ROS在这一过程中的作用。使用特异性ROS清除剂的研究进一步表明，羟基自由基，而不是过氧化氢或超氧阴离子，是顺铂细胞凋亡作用的主要氧化物质。电子自旋共振研究证实顺铂诱导羟基自由基的形成。羟基自由基介导顺铂细胞凋亡的机制可能与通过泛素-蛋白酶体降解下调抗凋亡蛋白Bcl-2有关。Bcl-2对羟基自由基也有负调控作用。综上所述，我们的研究结果表明，羟基自由基通过Bcl-2调控在顺铂诱导的毛囊细胞死亡中发挥了重要作用。由于CIA是顺铂和许多其他化疗药物的主要副作用，目前尚无有效的治疗方法，因此从本研究中获得的知识可用于通过局部治疗而不影响化疗效果的CIA预防性治疗策略的设计。
Induction of massive apoptosis of hair follicle cells by chemotherapy has been implicated in the pathogenesis of chemotherapy-induced alopecia (CIA), but the underlying mechanisms of regulation are not well understood. The present study investigated the apoptotic effect of cisplatin in human hair follicle dermal papilla cells and HaCaT keratinocytes, and determined the identity and role of specific reactive oxygen species (ROS) involved in the process. Treatment of the cells with cisplatin induced ROS generation and a parallel increase in caspase activation and apoptotic cell death. Inhibition of ROS generation by antioxidants inhibited the apoptotic effect of cisplatin, indicating the role of ROS in the process. Studies using specific ROS scavengers further showed that hydroxyl radical, but not hydrogen peroxide or superoxide anion, is the primary oxidative species responsible for the apoptotic effect of cisplatin. Electron spin resonance studies confirmed the formation of hydroxyl radicals induced by cisplatin. The mechanism by which hydroxyl radical mediates the apoptotic effect of cisplatin was shown to involve down-regulation of the anti-apoptotic protein Bcl-2 through ubiquitin-proteasomal degradation. Bcl-2 was also shown to have a negative regulatory role on hydroxyl radical. Together, our results indicate an essential role of hydroxyl radical in cisplatin-induced cell death of hair follicle cells through Bcl-2 regulation. Since CIA is a major side effect of cisplatin and many other chemotherapeutic agents with no known effective treatments, the knowledge gained from this study could be useful in the design of preventive treatment strategies for CIA through localized therapy without compromising the chemotherapy efficacy.
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影响因子：
3.8
作者：
McFadden, SL;Ding, DL;Salvi, RJ
通讯作者：
Salvi, RJ
影响因子：
11.2
作者：
Chanvorachote, Pithi;Nimmannit, Ubonthip;Rojanasakul, Yon
通讯作者：
Rojanasakul, Yon
影响因子：
4.6
作者：
Inui, S;Itami, S;Chang, CS
通讯作者：
Chang, CS
影响因子：
64.5
作者：
Li, P;Nijhawan, D;Wang, XD
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Wang, XD
影响因子：
3.1
作者：
Haendeler, J;Messmer, UK;Dimmeler, S
通讯作者：
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