9-cis retinoic acid is the ALDH1A1 product that stimulates melanogenesis.
9-cis retinoic acid is the ALDH1A1 product that stimulates melanogenesis.
复制标题
DOI：
10.1111/exd.12099
复制
发表时间：
2013-03
影响因子：
3.6
通讯作者：
Ganesan AK
中科院分区：
文献类型：
--
作者：
Paterson EK;Ho H;Kapadia R;Ganesan AK
醛脱氢酶1A 1（ALDH 1A 1）是一种催化脂质醛转化为脂质羧酸的酶，在抗紫外线辐射、黑素生成和干细胞维持中起多效性作用。在这项研究中，RNAi和药理学方法的组合被用来确定哪些ALDH 1A 1底物和产物调节黑素生成。最初的研究表明，无论是紫外线诱导的脂质醛4-羟基-2-壬烯醛或ALDH 1A 1的产品全反式视黄酸明显诱导黑素生成。相比之下，ALDH 1A 1底物9-顺式视网膜及其相应产物9-顺式视黄酸均有效诱导MITF mRNA、酪氨酸酶mRNA和黑色素的积累。ALDH 1A 1耗竭抑制9-顺式视黄醛而不是9-顺式视黄酸刺激黑素生成的能力，表明ALDH 1A 1通过催化9-顺式视黄醛转化为9-顺式视黄酸来调节黑素生成。添加有效的ALDH 1A抑制剂（氨腈或Angeli盐）抑制酪氨酸酶和MITF mRNA在体外的积累，以及黑色素在皮肤等同物中的积累，表明9-顺式类维生素A调节完整表皮中的黑色素生成。总之，这些研究不仅确定了氰胺作为一种潜在的新的治疗色素沉着症，但也确定9-顺式视黄酸作为色素刺激剂，可能有临床效用，在治疗色素减退症，如白癜风。
Aldehyde dehydrogenase 1A1 (ALDH1A1), an enzyme that catalyzes the conversion of lipid aldehydes to lipid carboxylic acids, plays pleiotropic roles in UV-radiation resistance, melanogenesis, and stem cell maintenance. In this study, a combination of RNAi and pharmacologic approaches were used to determine which ALDH1A1 substrates and products regulate melanogenesis. Initial studies revealed that neither the UV-induced lipid aldehyde 4-hydroxy-2-nonenal nor the ALDH1A1 product all-trans retinoic acid appreciably induced melanogenesis. In contrast, both the ALDH1A1 substrate 9-cis retinal and its corresponding product 9-cis retinoic acid potently induced the accumulation of MITF mRNA, Tyrosinase mRNA, and melanin. ALDH1A1 depletion inhibited the ability of 9-cis retinal but not 9-cis retinoic acid to stimulate melanogenesis, indicating that ALDH1A1 regulates melanogenesis by catalyzing the conversion of 9-cis retinal to 9-cis retinoic acid. The addition of potent ALDH1A inhibitors (cyanamide or Angeli’s salt) suppressed Tyrosinase and MITF mRNA accumulation in vitro and also melanin accumulation in skin equivalents, suggesting that 9-cis retinoids regulate melanogenesis in the intact epidermis. Taken together, these studies not only identify cyanamide as a potential novel treatment for hyperpigmentary disorders, but also identify 9-cis retinoic acid as a pigment stimulatory agent that may have clinical utility in the treatment of hypopigmentary disorders, such as vitiligo.
登录
查看更多内容
影响因子：
7.2
作者：
Goh, Myeong-Jin;Park, Jun-Seong;Na, Yong-Joo
通讯作者：
Na, Yong-Joo
影响因子：
64.5
作者：
HEYMAN, RA;MANGELSDORF, DJ;THALLER, C
通讯作者：
THALLER, C
影响因子：
3.4
作者：
Chen, Ying;Koppaka, Vindhya;Thompson, David C.;Vasiliou, Vasilis
通讯作者：
Vasiliou, Vasilis
影响因子：
10.5
作者：
Calleja, Cecile;Messaddeq, Nadia;Chambon, Pierre
通讯作者：
Chambon, Pierre
影响因子：
4.1
作者：
HOLICK, MF
通讯作者：
HOLICK, MF