Cadmium induces retinoic acid signaling by regulating retinoic acid metabolic gene expression.
نویسندگان
چکیده
The transition metal cadmium is an environmental teratogen. In addition, cadmium and retinoic acid can act synergistically to induce forelimb malformations. The molecular mechanism underlying the teratogenicity of cadmium and the synergistic effect with retinoic acid has not been addressed. An evolutionarily conserved gene, beta,beta-carotene 15,15'-monooxygenase (BCMO), which is involved in retinoic acid biosynthesis, was studied in both Caenorhabditis elegans and murine Hepa 1-6 cells. In C. elegans, bcmo-1 was expressed in the intestine and was cadmium inducible. Similarly, in Hepa 1-6 cells, Bcmo1 was induced by cadmium. Retinoic acid-mediated signaling increased after 24-h exposures to 5 and 10 microm cadmium in Hepa 1-6 cells. Examination of gene expression demonstrated that the induction of retinoic acid signaling by cadmium may be mediated by overexpression of Bcmo1. Furthermore, cadmium inhibited the expression of Cyp26a1 and Cyp26b1, which are involved in retinoic acid degradation. These results indicate that cadmium-induced teratogenicity may be due to the ability of the metal to increase the levels of retinoic acid by disrupting the expression of retinoic acid-metabolizing genes.
منابع مشابه
9-cis-Retinoic Acid and 1,25-dihydroxy Vitamin D3 Improve the Differentiation of Neural Stem Cells into Oligodendrocytes through the Inhibition of the Notch and Wnt Signaling Pathways
Background: Differentiating oligodendrocyte precursor cells (OPCs) into oligodendrocytes could be improved by inhibiting signaling pathways such as Wnt and Notch. 9-cis-retinoic acid (9-cis-RA) and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) can ameliorate oligodendrogenesis. We investigated whether they could increase oligodendrogenesis by inhibiting the Wnt and Notch signaling pathways.Methods: Co...
متن کاملAll-trans Retinoic Acid Regulates the Balance of Treg-Th17 Cells through ERK and P38 Signaling Pathway
متن کامل
The Effect of Retinoic Acid on Seminal Vesicle Epithelial Cell
Purpose: The seminal vesicles are androgen dependent exocrine glands producing protein-rich secretion. The retinoic acid has been implicated as a signaling molecule for the seminal vesicle development. In the present study, the effect of retinoic acid on seminal vesicle epithelial cell of neonatal mouse was investigated. Materials and Methods: Newborn male N-MRI mice were injected intraperiton...
متن کاملAnalysis of Promyelocytic Leukemia in Human Embryonic Carcinoma Stem Cells During Retinoic Acid-Induced Neural Differentiation
Background: Promyelocytic leukemia protein (PML) is a tumor suppressor protein that is involved in myeloid cell differentiation in response to retinoic acid (RA). In addition, RA acts as a natural morphogen in neural development. Objectives: This study aimed to examine PML gene expression in different stages of in vitro neural differentiation of NT2 cells, and to investigate the possible role o...
متن کاملRetinoic Acid Determines the Fate of Spermatogonia
In this review, we aim to examine the effect of extrinsic and intrinsic factors on spermatogenesis process taking into account a complex signaling pathway. Primarily, it is suggested that retinoic acid (RA) has a vital function in spermatogenesis process and it is considered to be essential for completion of spermatogonia into mature spermatozoa. In the present review, the key effects of retino...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 284 37 شماره
صفحات -
تاریخ انتشار 2009