Modulation of VEGF production by pH and glucose in retinal Muller cells

Steven E. Brooks, Xiaolin Gu, Paul M. Kaufmann, Dennis M. Marcus, Ruth B Caldwell

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Purpose. To investigate the influence of pH and glucose concentration, both of which represent significant biochemical variables in tissue ischemia, on the production of VEGF protein by retinal Muller cells and C6 glioma cells, under normoxic and hypoxic conditions. Methods. Rat retinal Muller cells and C6 glioma cells grown in tissue culture monolayers were studied. The effect of pH (range 7.0-8.0) and glucose concentration (0.6-25 mmol/L) on VEGF protein production, under both normoxic and hypoxic conditions, were evaluated by ELISA analysis of the conditioned media. Establishment of significant cell hypoxia was verified by measurement of lactate release into the conditioned media. Results. Hypoxia caused a 7.9-fold increase in VEGF production in C6 cells at 24 h, and a 3.4-fold increase in Muller cells after 48 h. Under hypoxic conditions, VEGF protein production was increased further by increasing pH and increasing glucose, and decreased by low pH and low glucose. Varying the glucose concentration or pH of the medium did not result in significant induction of VEGF protein production by either cell type under normoxic conditions. Conclusions. Both glucose and pH significantly affected VEGF production induced by low oxygen. However, neither exerted a measurable stimulatory effect on VEGF production in normoxic conditions. Coexisting hypoxia and acidosis or hypoglycemia, as might occur in severe tissue ischemia, may render glial cells incapable of effectively upregulating VEGF synthesis, while alkalosis or hyperglycemia may augment hypoxia-induced VEGF production.

Original languageEnglish (US)
Pages (from-to)875-882
Number of pages8
JournalCurrent Eye Research
Volume17
Issue number9
DOIs
StatePublished - Sep 29 1998

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Ependymoglial Cells
Vascular Endothelial Growth Factor A
Glucose
Conditioned Culture Medium
Glioma
Proteins
Ischemia
Cell Hypoxia
Alkalosis
Acidosis
Hypoglycemia
Neuroglia
Hyperglycemia
Lactic Acid
Enzyme-Linked Immunosorbent Assay
Oxygen

Keywords

  • Glucose
  • Hypoxia
  • Muller cells
  • Rat
  • Vascular endothelial growth factor (VEGF)
  • pH

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Modulation of VEGF production by pH and glucose in retinal Muller cells. / Brooks, Steven E.; Gu, Xiaolin; Kaufmann, Paul M.; Marcus, Dennis M.; Caldwell, Ruth B.

In: Current Eye Research, Vol. 17, No. 9, 29.09.1998, p. 875-882.

Research output: Contribution to journalArticle

Brooks, Steven E. ; Gu, Xiaolin ; Kaufmann, Paul M. ; Marcus, Dennis M. ; Caldwell, Ruth B. / Modulation of VEGF production by pH and glucose in retinal Muller cells. In: Current Eye Research. 1998 ; Vol. 17, No. 9. pp. 875-882.
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abstract = "Purpose. To investigate the influence of pH and glucose concentration, both of which represent significant biochemical variables in tissue ischemia, on the production of VEGF protein by retinal Muller cells and C6 glioma cells, under normoxic and hypoxic conditions. Methods. Rat retinal Muller cells and C6 glioma cells grown in tissue culture monolayers were studied. The effect of pH (range 7.0-8.0) and glucose concentration (0.6-25 mmol/L) on VEGF protein production, under both normoxic and hypoxic conditions, were evaluated by ELISA analysis of the conditioned media. Establishment of significant cell hypoxia was verified by measurement of lactate release into the conditioned media. Results. Hypoxia caused a 7.9-fold increase in VEGF production in C6 cells at 24 h, and a 3.4-fold increase in Muller cells after 48 h. Under hypoxic conditions, VEGF protein production was increased further by increasing pH and increasing glucose, and decreased by low pH and low glucose. Varying the glucose concentration or pH of the medium did not result in significant induction of VEGF protein production by either cell type under normoxic conditions. Conclusions. Both glucose and pH significantly affected VEGF production induced by low oxygen. However, neither exerted a measurable stimulatory effect on VEGF production in normoxic conditions. Coexisting hypoxia and acidosis or hypoglycemia, as might occur in severe tissue ischemia, may render glial cells incapable of effectively upregulating VEGF synthesis, while alkalosis or hyperglycemia may augment hypoxia-induced VEGF production.",
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N2 - Purpose. To investigate the influence of pH and glucose concentration, both of which represent significant biochemical variables in tissue ischemia, on the production of VEGF protein by retinal Muller cells and C6 glioma cells, under normoxic and hypoxic conditions. Methods. Rat retinal Muller cells and C6 glioma cells grown in tissue culture monolayers were studied. The effect of pH (range 7.0-8.0) and glucose concentration (0.6-25 mmol/L) on VEGF protein production, under both normoxic and hypoxic conditions, were evaluated by ELISA analysis of the conditioned media. Establishment of significant cell hypoxia was verified by measurement of lactate release into the conditioned media. Results. Hypoxia caused a 7.9-fold increase in VEGF production in C6 cells at 24 h, and a 3.4-fold increase in Muller cells after 48 h. Under hypoxic conditions, VEGF protein production was increased further by increasing pH and increasing glucose, and decreased by low pH and low glucose. Varying the glucose concentration or pH of the medium did not result in significant induction of VEGF protein production by either cell type under normoxic conditions. Conclusions. Both glucose and pH significantly affected VEGF production induced by low oxygen. However, neither exerted a measurable stimulatory effect on VEGF production in normoxic conditions. Coexisting hypoxia and acidosis or hypoglycemia, as might occur in severe tissue ischemia, may render glial cells incapable of effectively upregulating VEGF synthesis, while alkalosis or hyperglycemia may augment hypoxia-induced VEGF production.

AB - Purpose. To investigate the influence of pH and glucose concentration, both of which represent significant biochemical variables in tissue ischemia, on the production of VEGF protein by retinal Muller cells and C6 glioma cells, under normoxic and hypoxic conditions. Methods. Rat retinal Muller cells and C6 glioma cells grown in tissue culture monolayers were studied. The effect of pH (range 7.0-8.0) and glucose concentration (0.6-25 mmol/L) on VEGF protein production, under both normoxic and hypoxic conditions, were evaluated by ELISA analysis of the conditioned media. Establishment of significant cell hypoxia was verified by measurement of lactate release into the conditioned media. Results. Hypoxia caused a 7.9-fold increase in VEGF production in C6 cells at 24 h, and a 3.4-fold increase in Muller cells after 48 h. Under hypoxic conditions, VEGF protein production was increased further by increasing pH and increasing glucose, and decreased by low pH and low glucose. Varying the glucose concentration or pH of the medium did not result in significant induction of VEGF protein production by either cell type under normoxic conditions. Conclusions. Both glucose and pH significantly affected VEGF production induced by low oxygen. However, neither exerted a measurable stimulatory effect on VEGF production in normoxic conditions. Coexisting hypoxia and acidosis or hypoglycemia, as might occur in severe tissue ischemia, may render glial cells incapable of effectively upregulating VEGF synthesis, while alkalosis or hyperglycemia may augment hypoxia-induced VEGF production.

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