Acute cholesterol depletion leads to net loss of the organic osmolyte taurine in Ehrlich Lettré tumor cells
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Acute cholesterol depletion leads to net loss of the organic osmolyte taurine in Ehrlich Lettré tumor cells. / Villumsen, Kasper Rømer; Duelund, Lars; Lambert, Ian Henry.
I: Amino Acids, Bind 39, Nr. 5, 01.11.2010, s. 1521-36.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Acute cholesterol depletion leads to net loss of the organic osmolyte taurine in Ehrlich Lettré tumor cells
AU - Villumsen, Kasper Rømer
AU - Duelund, Lars
AU - Lambert, Ian Henry
PY - 2010/11/1
Y1 - 2010/11/1
N2 - In mammalian cells, the organic osmolyte taurine is accumulated by the Na-dependent taurine transporter TauT and released though the volume- and DIDS-sensitive organic anion channel. Incubating Ehrlich Lettré tumor cells with methyl-ß-cyclodextrin (5 mM, 1 h) reduces the total cholesterol pool to 60±5% of the control value. Electron spin resonance data indicate a concomitant disruption of cholesterol-rich micro-domains. Active taurine uptake, cellular taurine content, and cell volume are reduced by 50, 20 and 20% compared to control values, respectively, whereas the passive taurine release is increased 4.5-fold under isotonic conditions following cholesterol depletion. However, taurine release under isotonic conditions is insensitive to DIDS and inhibitors of the volume-regulated anion channel. Uptake and release of meAIB are similarly affected following cholesterol depletion. Kinetic analysis reveals that cholesterol depletion increases TauT's affinity toward taurine but reduces its maximal transport capacity. Cholesterol depletion has no impact on TauT regulation by protein kinases A and C. Phospholipase A2 activity, which is required for the activation of volume-sensitive organic anion channel (VSOAC), is increased under isotonic and hypotonic conditions following cholesterol depletion, whereas taurine release under hypotonic conditions is reduced following cholesterol depletion. Hence, acute cholesterol depletion of Ehrlich Lettré cells leads to reduced TauT and VSOAC activities and at the same time increases the release of organic osmolytes via a leak pathway different from the volume-sensitive pathways for amino acids and anions.
AB - In mammalian cells, the organic osmolyte taurine is accumulated by the Na-dependent taurine transporter TauT and released though the volume- and DIDS-sensitive organic anion channel. Incubating Ehrlich Lettré tumor cells with methyl-ß-cyclodextrin (5 mM, 1 h) reduces the total cholesterol pool to 60±5% of the control value. Electron spin resonance data indicate a concomitant disruption of cholesterol-rich micro-domains. Active taurine uptake, cellular taurine content, and cell volume are reduced by 50, 20 and 20% compared to control values, respectively, whereas the passive taurine release is increased 4.5-fold under isotonic conditions following cholesterol depletion. However, taurine release under isotonic conditions is insensitive to DIDS and inhibitors of the volume-regulated anion channel. Uptake and release of meAIB are similarly affected following cholesterol depletion. Kinetic analysis reveals that cholesterol depletion increases TauT's affinity toward taurine but reduces its maximal transport capacity. Cholesterol depletion has no impact on TauT regulation by protein kinases A and C. Phospholipase A2 activity, which is required for the activation of volume-sensitive organic anion channel (VSOAC), is increased under isotonic and hypotonic conditions following cholesterol depletion, whereas taurine release under hypotonic conditions is reduced following cholesterol depletion. Hence, acute cholesterol depletion of Ehrlich Lettré cells leads to reduced TauT and VSOAC activities and at the same time increases the release of organic osmolytes via a leak pathway different from the volume-sensitive pathways for amino acids and anions.
KW - Animals
KW - Carcinoma, Ehrlich Tumor
KW - Cholesterol
KW - Ion Channels
KW - Membrane Glycoproteins
KW - Membrane Transport Proteins
KW - Mice
KW - Osmosis
KW - Phospholipases A2
KW - Taurine
KW - Tumor Cells, Cultured
KW - beta-Cyclodextrins
U2 - 10.1007/s00726-010-0621-4
DO - 10.1007/s00726-010-0621-4
M3 - Journal article
C2 - 20499258
VL - 39
SP - 1521
EP - 1536
JO - Amino Acids
JF - Amino Acids
SN - 0939-4451
IS - 5
ER -
ID: 33884623