TY - JOUR
T1 - Intracellular glutathione deficiency is associated with enhanced nuclear factor-κB activation in older non-insulin dependent diabetic patients
AU - Arnalich, Francisco M.
AU - Hernanz, Angel
AU - López-Maderuelo, Dolores
AU - De La Fuente, Mónica
AU - Andrés-Mateos, Eva
AU - Fernández-Capitán, Carmen
AU - Montiel, Carmen
PY - 2001/1/1
Y1 - 2001/1/1
N2 - Diabetes mellitus may be associated with intracellular glutathione (GSH) deficiency. Since in vivo studies have shown that plasma intracellular GSH plays a key role in regulating the activation of nuclear factor κB (NF-κB), we have investigated the relationship between intracellular thiols (GSH, homocysteine, cysteine and cysteinyglycine) and NF-κB activity in the peripheral blood mononuclear cells (PBMC) of 63 elderly non-insulin dependent diabetes mellitus (NIDDM) patients (28 microalbuminurics and 35 normoalbuminurics) and 30 healthy age- and sex-matched subjects. In addition, we have measured plasma concentrations of these thiol compounds, serum concentrations of interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (sVCAM-1), that are partly dependent on the NF-κB activation, as well as the serum levels of thiobarbituric acid reacting substances (TBARS), as index of lipid peroxidation. Diabetic patients with microalbuminuria (MAB) and normoalbuminuria had NF-κB activity 2.1- and 1.5-fold greater, respectively, than the control group. As compared to normoalbuminuric patients, patients with MAB had significantly higher levels of glycemia, plasma homocysteine, and serum concentrations of TBARS, IL-6 and sVCAM-1 (in all cases, p < 0.01), and significantly lower GSH content in the PBMC (p < 0.05). The intracellular GSH in PBMC correlated with NF-κB activation (r = - 0.82; p < 0.0001), serum TBARS (r=-0.60; p<0.001), and with fasting glycemia (r = - 0.56; p < 0.001) in patients with MAB, whereas a weaker association between GSH levels in PBMC and NF-κB activation (r = - 0.504, p < 0.001) was seen in patients without MAB. These results suggest that the decrease of intracellular GSH content in elderly NIDDM patients with MAB is strongly associated with enhanced NF-κB activation, which could contribute to the development of increased glomerular capillary permeability and its rapid progression.
AB - Diabetes mellitus may be associated with intracellular glutathione (GSH) deficiency. Since in vivo studies have shown that plasma intracellular GSH plays a key role in regulating the activation of nuclear factor κB (NF-κB), we have investigated the relationship between intracellular thiols (GSH, homocysteine, cysteine and cysteinyglycine) and NF-κB activity in the peripheral blood mononuclear cells (PBMC) of 63 elderly non-insulin dependent diabetes mellitus (NIDDM) patients (28 microalbuminurics and 35 normoalbuminurics) and 30 healthy age- and sex-matched subjects. In addition, we have measured plasma concentrations of these thiol compounds, serum concentrations of interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (sVCAM-1), that are partly dependent on the NF-κB activation, as well as the serum levels of thiobarbituric acid reacting substances (TBARS), as index of lipid peroxidation. Diabetic patients with microalbuminuria (MAB) and normoalbuminuria had NF-κB activity 2.1- and 1.5-fold greater, respectively, than the control group. As compared to normoalbuminuric patients, patients with MAB had significantly higher levels of glycemia, plasma homocysteine, and serum concentrations of TBARS, IL-6 and sVCAM-1 (in all cases, p < 0.01), and significantly lower GSH content in the PBMC (p < 0.05). The intracellular GSH in PBMC correlated with NF-κB activation (r = - 0.82; p < 0.0001), serum TBARS (r=-0.60; p<0.001), and with fasting glycemia (r = - 0.56; p < 0.001) in patients with MAB, whereas a weaker association between GSH levels in PBMC and NF-κB activation (r = - 0.504, p < 0.001) was seen in patients without MAB. These results suggest that the decrease of intracellular GSH content in elderly NIDDM patients with MAB is strongly associated with enhanced NF-κB activation, which could contribute to the development of increased glomerular capillary permeability and its rapid progression.
KW - Aging
KW - Glutathione
KW - Lipid peroxides (TBARS)
KW - Non-insulin-dependent diabetes mellitus
KW - Nuclear factor κB
KW - Oxidative stress
KW - Peripheral blood mononuclear cells
KW - Thiol compounds
UR - https://www.scopus.com/pages/publications/0035689644
U2 - 10.1080/10715760100301371
DO - 10.1080/10715760100301371
M3 - Article
C2 - 11811538
AN - SCOPUS:0035689644
SN - 1071-5762
VL - 35
SP - 873
EP - 884
JO - Free Radical Research
JF - Free Radical Research
IS - 6
ER -
