Hypoxia augments TNF-α-mediated endothelin-1 release and cell proliferation in human optic nerve head astrocytes

Devashish Desai, Shaoqing He, Thomas Yorio, Raghu Krishnamoorthy, Ganesh Prasanna

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Abstract

The effect of hypoxia (24h) on TNF-α-mediated release of endothelin-1 (ET-1) from human optic nerve head astrocytes (hONAs) and TNF-α- and ET-1-induced hONA proliferation was determined. ET-1 synthesis and release was quantitated using ELISA while TNF-α (10nM)- and ET-1 (100nM)-mediated hONA proliferation was assessed by CellTiter 96 aqueous one-solution cell proliferation assay, respectively. hONAs appeared to be more rounded with fewer processes following 24h hypoxia compared to thodr seen in normoxia. Hypoxia enhanced TNF-α-mediated ET-1 synthesis and release (by 5-fold) and also significantly increased TNF-α- and ET-1-mediated hONA proliferation. PD142893 (1μM), an ETA/B receptor antagonist, blocked ET-1-mediated hONA proliferation both under normoxia and hypoxia, while doing so only under normoxia following TNF-α treatment. Also, U0126 (10μM; an upstream ERK1/2 inhibitor) completely blocked agonist-induced hONA proliferation in normoxia and partially blocked the same in hypoxia. These results demonstrate for the first time that hONAs secrete ET-1 and that TNF-α and hypoxia can regulate its levels. Moreover, hypoxia augments the proliferative responses of hONAs to TNF-α and ET-1. These agonist-mediated effects following hypoxia could contribute to astroglial activation as seen in glaucomatous optic nerve heads.

Original languageEnglish
Pages (from-to)642-648
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume318
Issue number3
DOIs
StatePublished - 4 Jun 2004

Fingerprint

Optic Disk
Cell proliferation
Endothelin-1
Astrocytes
Optics
Cell Proliferation
Hypoxia
Assays
Chemical activation
Enzyme-Linked Immunosorbent Assay

Keywords

  • Astrogliosis
  • Endothelin-1
  • Glaucoma
  • Hypoxia
  • Optic nerve head
  • TNF-α

Cite this

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title = "Hypoxia augments TNF-α-mediated endothelin-1 release and cell proliferation in human optic nerve head astrocytes",
abstract = "The effect of hypoxia (24h) on TNF-α-mediated release of endothelin-1 (ET-1) from human optic nerve head astrocytes (hONAs) and TNF-α- and ET-1-induced hONA proliferation was determined. ET-1 synthesis and release was quantitated using ELISA while TNF-α (10nM)- and ET-1 (100nM)-mediated hONA proliferation was assessed by CellTiter 96 aqueous one-solution cell proliferation assay, respectively. hONAs appeared to be more rounded with fewer processes following 24h hypoxia compared to thodr seen in normoxia. Hypoxia enhanced TNF-α-mediated ET-1 synthesis and release (by 5-fold) and also significantly increased TNF-α- and ET-1-mediated hONA proliferation. PD142893 (1μM), an ETA/B receptor antagonist, blocked ET-1-mediated hONA proliferation both under normoxia and hypoxia, while doing so only under normoxia following TNF-α treatment. Also, U0126 (10μM; an upstream ERK1/2 inhibitor) completely blocked agonist-induced hONA proliferation in normoxia and partially blocked the same in hypoxia. These results demonstrate for the first time that hONAs secrete ET-1 and that TNF-α and hypoxia can regulate its levels. Moreover, hypoxia augments the proliferative responses of hONAs to TNF-α and ET-1. These agonist-mediated effects following hypoxia could contribute to astroglial activation as seen in glaucomatous optic nerve heads.",
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Hypoxia augments TNF-α-mediated endothelin-1 release and cell proliferation in human optic nerve head astrocytes. / Desai, Devashish; He, Shaoqing; Yorio, Thomas; Krishnamoorthy, Raghu; Prasanna, Ganesh.

In: Biochemical and Biophysical Research Communications, Vol. 318, No. 3, 04.06.2004, p. 642-648.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Hypoxia augments TNF-α-mediated endothelin-1 release and cell proliferation in human optic nerve head astrocytes

AU - Desai, Devashish

AU - He, Shaoqing

AU - Yorio, Thomas

AU - Krishnamoorthy, Raghu

AU - Prasanna, Ganesh

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N2 - The effect of hypoxia (24h) on TNF-α-mediated release of endothelin-1 (ET-1) from human optic nerve head astrocytes (hONAs) and TNF-α- and ET-1-induced hONA proliferation was determined. ET-1 synthesis and release was quantitated using ELISA while TNF-α (10nM)- and ET-1 (100nM)-mediated hONA proliferation was assessed by CellTiter 96 aqueous one-solution cell proliferation assay, respectively. hONAs appeared to be more rounded with fewer processes following 24h hypoxia compared to thodr seen in normoxia. Hypoxia enhanced TNF-α-mediated ET-1 synthesis and release (by 5-fold) and also significantly increased TNF-α- and ET-1-mediated hONA proliferation. PD142893 (1μM), an ETA/B receptor antagonist, blocked ET-1-mediated hONA proliferation both under normoxia and hypoxia, while doing so only under normoxia following TNF-α treatment. Also, U0126 (10μM; an upstream ERK1/2 inhibitor) completely blocked agonist-induced hONA proliferation in normoxia and partially blocked the same in hypoxia. These results demonstrate for the first time that hONAs secrete ET-1 and that TNF-α and hypoxia can regulate its levels. Moreover, hypoxia augments the proliferative responses of hONAs to TNF-α and ET-1. These agonist-mediated effects following hypoxia could contribute to astroglial activation as seen in glaucomatous optic nerve heads.

AB - The effect of hypoxia (24h) on TNF-α-mediated release of endothelin-1 (ET-1) from human optic nerve head astrocytes (hONAs) and TNF-α- and ET-1-induced hONA proliferation was determined. ET-1 synthesis and release was quantitated using ELISA while TNF-α (10nM)- and ET-1 (100nM)-mediated hONA proliferation was assessed by CellTiter 96 aqueous one-solution cell proliferation assay, respectively. hONAs appeared to be more rounded with fewer processes following 24h hypoxia compared to thodr seen in normoxia. Hypoxia enhanced TNF-α-mediated ET-1 synthesis and release (by 5-fold) and also significantly increased TNF-α- and ET-1-mediated hONA proliferation. PD142893 (1μM), an ETA/B receptor antagonist, blocked ET-1-mediated hONA proliferation both under normoxia and hypoxia, while doing so only under normoxia following TNF-α treatment. Also, U0126 (10μM; an upstream ERK1/2 inhibitor) completely blocked agonist-induced hONA proliferation in normoxia and partially blocked the same in hypoxia. These results demonstrate for the first time that hONAs secrete ET-1 and that TNF-α and hypoxia can regulate its levels. Moreover, hypoxia augments the proliferative responses of hONAs to TNF-α and ET-1. These agonist-mediated effects following hypoxia could contribute to astroglial activation as seen in glaucomatous optic nerve heads.

KW - Astrogliosis

KW - Endothelin-1

KW - Glaucoma

KW - Hypoxia

KW - Optic nerve head

KW - TNF-α

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DO - 10.1016/j.bbrc.2004.04.073

M3 - Article

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SP - 642

EP - 648

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 3

ER -