Oxygen sensing by H+: Implications for HIF and hypoxic cell memory

Karim Mekhail, Mireille Khacho, Lakshman Gunaratnam, Stephen Lee

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Hypoxia and acidosis are common features of several physiological and pathological situations, including cancer and stroke. The HIF (hypoxia-inducible factor) transcription factor plays a seminal role in orchestrating cellular responses to alterations in oxygen availability. HIF is degraded in normal oxygen tension by the VHL (von Hippel-Lindau) tumor suppressor protein but stabilized by hypoxia to activate an array of genes implicated in oxygen homeostasis including vascular endothelial growth factor. Cells respond to a comparatively mild decline in oxygen tension by converting to an anaerobic state of respiration and secreting lactic acid. We recently reported that a decrease in environmental pH triggers sequestration of VHL into the nucleolus neutralizing its ability to degrade HIF. This implies that cells have evolved a parallel mechanism of HIF activation that responds to changes in oxygen levels by sensing extracellular [H+]. Here we discuss the implications of this new VHL regulatory mechanism on oxygen homeostasis and hypoxic cell memory.

Original languageEnglish (US)
Pages (from-to)1027-1029
Number of pages3
JournalCell Cycle
Volume3
Issue number8
StatePublished - Aug 2004
Externally publishedYes

Fingerprint

Cells
Oxygen
Data storage equipment
Von Hippel-Lindau Tumor Suppressor Protein
Homeostasis
Acidosis
Vascular Endothelial Growth Factor A
Hypoxia
Lactic Acid
Respiration
Transcription Factors
Genes
Chemical activation
Stroke
Availability
Neoplasms

Keywords

  • Acidosis
  • Cancer
  • Cardiac arrest
  • HIF
  • Hypoxia
  • Nucleolus
  • pH
  • Stroke
  • VHL

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Mekhail, K., Khacho, M., Gunaratnam, L., & Lee, S. (2004). Oxygen sensing by H+: Implications for HIF and hypoxic cell memory. Cell Cycle, 3(8), 1027-1029.

Oxygen sensing by H+ : Implications for HIF and hypoxic cell memory. / Mekhail, Karim; Khacho, Mireille; Gunaratnam, Lakshman; Lee, Stephen.

In: Cell Cycle, Vol. 3, No. 8, 08.2004, p. 1027-1029.

Research output: Contribution to journalArticle

Mekhail, K, Khacho, M, Gunaratnam, L & Lee, S 2004, 'Oxygen sensing by H+: Implications for HIF and hypoxic cell memory', Cell Cycle, vol. 3, no. 8, pp. 1027-1029.
Mekhail K, Khacho M, Gunaratnam L, Lee S. Oxygen sensing by H+: Implications for HIF and hypoxic cell memory. Cell Cycle. 2004 Aug;3(8):1027-1029.
Mekhail, Karim ; Khacho, Mireille ; Gunaratnam, Lakshman ; Lee, Stephen. / Oxygen sensing by H+ : Implications for HIF and hypoxic cell memory. In: Cell Cycle. 2004 ; Vol. 3, No. 8. pp. 1027-1029.
@article{b5a03ed53e444ba9b6a19e80b1e2461e,
title = "Oxygen sensing by H+: Implications for HIF and hypoxic cell memory",
abstract = "Hypoxia and acidosis are common features of several physiological and pathological situations, including cancer and stroke. The HIF (hypoxia-inducible factor) transcription factor plays a seminal role in orchestrating cellular responses to alterations in oxygen availability. HIF is degraded in normal oxygen tension by the VHL (von Hippel-Lindau) tumor suppressor protein but stabilized by hypoxia to activate an array of genes implicated in oxygen homeostasis including vascular endothelial growth factor. Cells respond to a comparatively mild decline in oxygen tension by converting to an anaerobic state of respiration and secreting lactic acid. We recently reported that a decrease in environmental pH triggers sequestration of VHL into the nucleolus neutralizing its ability to degrade HIF. This implies that cells have evolved a parallel mechanism of HIF activation that responds to changes in oxygen levels by sensing extracellular [H+]. Here we discuss the implications of this new VHL regulatory mechanism on oxygen homeostasis and hypoxic cell memory.",
keywords = "Acidosis, Cancer, Cardiac arrest, HIF, Hypoxia, Nucleolus, pH, Stroke, VHL",
author = "Karim Mekhail and Mireille Khacho and Lakshman Gunaratnam and Stephen Lee",
year = "2004",
month = "8",
language = "English (US)",
volume = "3",
pages = "1027--1029",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "8",

}

TY - JOUR

T1 - Oxygen sensing by H+

T2 - Implications for HIF and hypoxic cell memory

AU - Mekhail, Karim

AU - Khacho, Mireille

AU - Gunaratnam, Lakshman

AU - Lee, Stephen

PY - 2004/8

Y1 - 2004/8

N2 - Hypoxia and acidosis are common features of several physiological and pathological situations, including cancer and stroke. The HIF (hypoxia-inducible factor) transcription factor plays a seminal role in orchestrating cellular responses to alterations in oxygen availability. HIF is degraded in normal oxygen tension by the VHL (von Hippel-Lindau) tumor suppressor protein but stabilized by hypoxia to activate an array of genes implicated in oxygen homeostasis including vascular endothelial growth factor. Cells respond to a comparatively mild decline in oxygen tension by converting to an anaerobic state of respiration and secreting lactic acid. We recently reported that a decrease in environmental pH triggers sequestration of VHL into the nucleolus neutralizing its ability to degrade HIF. This implies that cells have evolved a parallel mechanism of HIF activation that responds to changes in oxygen levels by sensing extracellular [H+]. Here we discuss the implications of this new VHL regulatory mechanism on oxygen homeostasis and hypoxic cell memory.

AB - Hypoxia and acidosis are common features of several physiological and pathological situations, including cancer and stroke. The HIF (hypoxia-inducible factor) transcription factor plays a seminal role in orchestrating cellular responses to alterations in oxygen availability. HIF is degraded in normal oxygen tension by the VHL (von Hippel-Lindau) tumor suppressor protein but stabilized by hypoxia to activate an array of genes implicated in oxygen homeostasis including vascular endothelial growth factor. Cells respond to a comparatively mild decline in oxygen tension by converting to an anaerobic state of respiration and secreting lactic acid. We recently reported that a decrease in environmental pH triggers sequestration of VHL into the nucleolus neutralizing its ability to degrade HIF. This implies that cells have evolved a parallel mechanism of HIF activation that responds to changes in oxygen levels by sensing extracellular [H+]. Here we discuss the implications of this new VHL regulatory mechanism on oxygen homeostasis and hypoxic cell memory.

KW - Acidosis

KW - Cancer

KW - Cardiac arrest

KW - HIF

KW - Hypoxia

KW - Nucleolus

KW - pH

KW - Stroke

KW - VHL

UR - http://www.scopus.com/inward/record.url?scp=13944277272&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13944277272&partnerID=8YFLogxK

M3 - Article

C2 - 15280664

AN - SCOPUS:13944277272

VL - 3

SP - 1027

EP - 1029

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 8

ER -