Tags

Type your tag names separated by a space and hit enter

Endothelin-1 (ET-1) causes death of retinal neurons through activation of nitric oxide synthase (NOS) and production of superoxide anion.
Exp Eye Res. 2008 Jan; 86(1):118-30.EE

Abstract

Endothelin-1 (ET-1) is the most potent and long-acting vasoconstricting peptide presently known. In addition to its vascular effects, endothelin signaling pathway exists in the central nervous system (CNS), which is deeply related to neuronal degeneration. In the present study, we evaluated the effect of ET-1 on death of retinal neurons consisting mainly of amacrine cells, and its interaction with nitric oxide synthase (NOS) and superoxide production. Cultured retinal neurons from fetal rats were exposed to various doses of ET-1 (0.1, 1.0, 10 and 100nM). Neuronal toxicity of ET-1 was assessed by trypan blue exclusion, Hoechst 33,258 staining and TUNEL assay at different times. Intracellular levels of nitric oxide (NO), superoxide and peroxynitrite were determined semiquantitatively by DAF2-DA, hydroethidine and dihydrorhodamine-123, respectively. The effects of adding SOD (100U/ml) and L-NAME with ET-1 on these changes were evaluated. In addition, the receptor mechanisms involved in these reactions were determined by BQ-123 and BQ-788, receptor antagonists for ET A and ET B receptors, respectively. Exposure of cultured retinal neurons to ET-1 reduced the percentage of living cells in a dose- and time-dependent way, and the percentage of living cells was significantly increased by addition of SOD and L-NAME. Fluorometric analyses revealed that ET-1 increased the intracellular NO level in a dose- and time-dependent manner. The intracellular superoxide and peroxynitrite levels were also significantly increased 24h after incubation with 100nM of ET-1, and this elevation was suppressed by SOD and L-NAME. These ET-1-induced alterations were significantly suppressed when both BQ-123 and BQ-788 were added simultaneously with ET-1 to the medium. These results indicate that the neuronal death caused by ET-1 is most likely mediated by the activation of NOS in association with the formation of superoxides and peroxynitrite.

Authors+Show Affiliations

Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi Takatsuki Osaka, 569-8686 Japan. hidehirooku@aol.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17996868

Citation

Oku, Hidehiro, et al. "Endothelin-1 (ET-1) Causes Death of Retinal Neurons Through Activation of Nitric Oxide Synthase (NOS) and Production of Superoxide Anion." Experimental Eye Research, vol. 86, no. 1, 2008, pp. 118-30.
Oku H, Fukuhara M, Komori A, et al. Endothelin-1 (ET-1) causes death of retinal neurons through activation of nitric oxide synthase (NOS) and production of superoxide anion. Exp Eye Res. 2008;86(1):118-30.
Oku, H., Fukuhara, M., Komori, A., Okuno, T., Sugiyama, T., & Ikeda, T. (2008). Endothelin-1 (ET-1) causes death of retinal neurons through activation of nitric oxide synthase (NOS) and production of superoxide anion. Experimental Eye Research, 86(1), 118-30.
Oku H, et al. Endothelin-1 (ET-1) Causes Death of Retinal Neurons Through Activation of Nitric Oxide Synthase (NOS) and Production of Superoxide Anion. Exp Eye Res. 2008;86(1):118-30. PubMed PMID: 17996868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelin-1 (ET-1) causes death of retinal neurons through activation of nitric oxide synthase (NOS) and production of superoxide anion. AU - Oku,Hidehiro, AU - Fukuhara,Masayuki, AU - Komori,Asako, AU - Okuno,Takashi, AU - Sugiyama,Tetsuya, AU - Ikeda,Tsunehiko, Y1 - 2007/10/09/ PY - 2007/05/20/received PY - 2007/08/28/revised PY - 2007/10/03/accepted PY - 2007/11/13/pubmed PY - 2008/3/11/medline PY - 2007/11/13/entrez SP - 118 EP - 30 JF - Experimental eye research JO - Exp Eye Res VL - 86 IS - 1 N2 - Endothelin-1 (ET-1) is the most potent and long-acting vasoconstricting peptide presently known. In addition to its vascular effects, endothelin signaling pathway exists in the central nervous system (CNS), which is deeply related to neuronal degeneration. In the present study, we evaluated the effect of ET-1 on death of retinal neurons consisting mainly of amacrine cells, and its interaction with nitric oxide synthase (NOS) and superoxide production. Cultured retinal neurons from fetal rats were exposed to various doses of ET-1 (0.1, 1.0, 10 and 100nM). Neuronal toxicity of ET-1 was assessed by trypan blue exclusion, Hoechst 33,258 staining and TUNEL assay at different times. Intracellular levels of nitric oxide (NO), superoxide and peroxynitrite were determined semiquantitatively by DAF2-DA, hydroethidine and dihydrorhodamine-123, respectively. The effects of adding SOD (100U/ml) and L-NAME with ET-1 on these changes were evaluated. In addition, the receptor mechanisms involved in these reactions were determined by BQ-123 and BQ-788, receptor antagonists for ET A and ET B receptors, respectively. Exposure of cultured retinal neurons to ET-1 reduced the percentage of living cells in a dose- and time-dependent way, and the percentage of living cells was significantly increased by addition of SOD and L-NAME. Fluorometric analyses revealed that ET-1 increased the intracellular NO level in a dose- and time-dependent manner. The intracellular superoxide and peroxynitrite levels were also significantly increased 24h after incubation with 100nM of ET-1, and this elevation was suppressed by SOD and L-NAME. These ET-1-induced alterations were significantly suppressed when both BQ-123 and BQ-788 were added simultaneously with ET-1 to the medium. These results indicate that the neuronal death caused by ET-1 is most likely mediated by the activation of NOS in association with the formation of superoxides and peroxynitrite. SN - 0014-4835 UR - https://www.unboundmedicine.com/medline/citation/17996868/Endothelin_1__ET_1__causes_death_of_retinal_neurons_through_activation_of_nitric_oxide_synthase__NOS__and_production_of_superoxide_anion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(07)00279-5 DB - PRIME DP - Unbound Medicine ER -