Regulation of gene expression and secretory functions in oxygen-sensing pheochromocytoma cells

L. Conforti, S. Kobayashi, D. Beitner-Johnson, P. W. Conrad, T. Freeman, D. E. Millhorn

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The cellular response to hypoxia is complex. Specialized oxygen chemosensitive cells that are excitable respond to reduced O2 by membrane depolarization, altered gene expression, and neurotransmitter secretion. We have used the O2-sensitive pheochromocytoma (PC12) cell line to investigate the cellular response to hypoxia. Here, we present evidence that membrane depolarization and increased intracellular free Ca2+ are major regulatory events in these cells. Membrane depolarization is mediated by the inhibition of a slow-inactivating voltage-dependent potassium (K) channel. Evidence from molecular biology and patch-clamp studies indicate that the O2-sensitive K channel is a member of the Kv1 family. We also reviewed findings on the regulation of gene expression in PC12 cells during hypoxia. An increase in intracellular free Ca2+ is required for hypoxia-induced transcription of a number of genes including tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamine neurotransmitters, and several of the immediate early genes. We also reviewed the role of dopamine (DA) and adenosine (ADO) receptors in regulation of membrane depolarization and gene expression. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)249-260
Number of pages12
JournalRespiration Physiology
Volume115
Issue number2
DOIs
StatePublished - Apr 1 1999

Fingerprint

Gene Expression Regulation
Pheochromocytoma
PC12 Cells
Oxygen
Membranes
Neurotransmitter Agents
Gene Expression
Cell Hypoxia
Purinergic P1 Receptors
Immediate-Early Genes
Potassium Channels
Dopamine Receptors
Tyrosine 3-Monooxygenase
Catecholamines
Molecular Biology
Enzymes
Genes
Hypoxia

Keywords

  • Channels, K, oxygen-sensitive
  • Gene regulation, hypoxia
  • Hypoxia, cellular response, PC12
  • Pheochromocytoma cells, hypoxic response
  • Receptors, adenosine, dopamine

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine

Cite this

Regulation of gene expression and secretory functions in oxygen-sensing pheochromocytoma cells. / Conforti, L.; Kobayashi, S.; Beitner-Johnson, D.; Conrad, P. W.; Freeman, T.; Millhorn, D. E.

In: Respiration Physiology, Vol. 115, No. 2, 01.04.1999, p. 249-260.

Research output: Contribution to journalArticle

Conforti, L. ; Kobayashi, S. ; Beitner-Johnson, D. ; Conrad, P. W. ; Freeman, T. ; Millhorn, D. E. / Regulation of gene expression and secretory functions in oxygen-sensing pheochromocytoma cells. In: Respiration Physiology. 1999 ; Vol. 115, No. 2. pp. 249-260.
@article{cf4be04e75cc4479a9b3bbe613e9ea01,
title = "Regulation of gene expression and secretory functions in oxygen-sensing pheochromocytoma cells",
abstract = "The cellular response to hypoxia is complex. Specialized oxygen chemosensitive cells that are excitable respond to reduced O2 by membrane depolarization, altered gene expression, and neurotransmitter secretion. We have used the O2-sensitive pheochromocytoma (PC12) cell line to investigate the cellular response to hypoxia. Here, we present evidence that membrane depolarization and increased intracellular free Ca2+ are major regulatory events in these cells. Membrane depolarization is mediated by the inhibition of a slow-inactivating voltage-dependent potassium (K) channel. Evidence from molecular biology and patch-clamp studies indicate that the O2-sensitive K channel is a member of the Kv1 family. We also reviewed findings on the regulation of gene expression in PC12 cells during hypoxia. An increase in intracellular free Ca2+ is required for hypoxia-induced transcription of a number of genes including tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamine neurotransmitters, and several of the immediate early genes. We also reviewed the role of dopamine (DA) and adenosine (ADO) receptors in regulation of membrane depolarization and gene expression. Copyright (C) 1999 Elsevier Science B.V.",
keywords = "Channels, K, oxygen-sensitive, Gene regulation, hypoxia, Hypoxia, cellular response, PC12, Pheochromocytoma cells, hypoxic response, Receptors, adenosine, dopamine",
author = "L. Conforti and S. Kobayashi and D. Beitner-Johnson and Conrad, {P. W.} and T. Freeman and Millhorn, {D. E.}",
year = "1999",
month = "4",
day = "1",
doi = "10.1016/S0034-5687(99)00022-5",
language = "English (US)",
volume = "115",
pages = "249--260",
journal = "Respiratory Physiology and Neurobiology",
issn = "1569-9048",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Regulation of gene expression and secretory functions in oxygen-sensing pheochromocytoma cells

AU - Conforti, L.

AU - Kobayashi, S.

AU - Beitner-Johnson, D.

AU - Conrad, P. W.

AU - Freeman, T.

AU - Millhorn, D. E.

PY - 1999/4/1

Y1 - 1999/4/1

N2 - The cellular response to hypoxia is complex. Specialized oxygen chemosensitive cells that are excitable respond to reduced O2 by membrane depolarization, altered gene expression, and neurotransmitter secretion. We have used the O2-sensitive pheochromocytoma (PC12) cell line to investigate the cellular response to hypoxia. Here, we present evidence that membrane depolarization and increased intracellular free Ca2+ are major regulatory events in these cells. Membrane depolarization is mediated by the inhibition of a slow-inactivating voltage-dependent potassium (K) channel. Evidence from molecular biology and patch-clamp studies indicate that the O2-sensitive K channel is a member of the Kv1 family. We also reviewed findings on the regulation of gene expression in PC12 cells during hypoxia. An increase in intracellular free Ca2+ is required for hypoxia-induced transcription of a number of genes including tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamine neurotransmitters, and several of the immediate early genes. We also reviewed the role of dopamine (DA) and adenosine (ADO) receptors in regulation of membrane depolarization and gene expression. Copyright (C) 1999 Elsevier Science B.V.

AB - The cellular response to hypoxia is complex. Specialized oxygen chemosensitive cells that are excitable respond to reduced O2 by membrane depolarization, altered gene expression, and neurotransmitter secretion. We have used the O2-sensitive pheochromocytoma (PC12) cell line to investigate the cellular response to hypoxia. Here, we present evidence that membrane depolarization and increased intracellular free Ca2+ are major regulatory events in these cells. Membrane depolarization is mediated by the inhibition of a slow-inactivating voltage-dependent potassium (K) channel. Evidence from molecular biology and patch-clamp studies indicate that the O2-sensitive K channel is a member of the Kv1 family. We also reviewed findings on the regulation of gene expression in PC12 cells during hypoxia. An increase in intracellular free Ca2+ is required for hypoxia-induced transcription of a number of genes including tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamine neurotransmitters, and several of the immediate early genes. We also reviewed the role of dopamine (DA) and adenosine (ADO) receptors in regulation of membrane depolarization and gene expression. Copyright (C) 1999 Elsevier Science B.V.

KW - Channels, K, oxygen-sensitive

KW - Gene regulation, hypoxia

KW - Hypoxia, cellular response, PC12

KW - Pheochromocytoma cells, hypoxic response

KW - Receptors, adenosine, dopamine

UR - http://www.scopus.com/inward/record.url?scp=0032965705&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032965705&partnerID=8YFLogxK

U2 - 10.1016/S0034-5687(99)00022-5

DO - 10.1016/S0034-5687(99)00022-5

M3 - Article

C2 - 10385038

AN - SCOPUS:0032965705

VL - 115

SP - 249

EP - 260

JO - Respiratory Physiology and Neurobiology

JF - Respiratory Physiology and Neurobiology

SN - 1569-9048

IS - 2

ER -