TY - JOUR
T1 - GSH protects against oxidative stress and toxicity in VL-17A cells exposed to high glucose
AU - Kumar, S. Mathan
AU - Swaminathan, Kavitha
AU - Clemens, Dahn L.
AU - Dey, Aparajita
N1 - Funding Information:
AD acknowledges the financial support received from Department of Biotechnology, New Delhi, India (Rapid Grant for Young Investigators). DLC was supported by a grant from the Veterans Administration. KS is grateful to Council of Scientific and Industrial Research (CSIR), New Delhi, India for awarding the Junior and Senior Research Fellowships. We thank Dr. BM Jaffar Ali, Life Sciences Division, AU-KBC Research Centre, Chennai, India for his kind suggestions as a Co-PI in the DBT sponsored project. We thank Dr. Suvro Chatterjee, Life Sciences Division, AU-KBC Research Centre, Chennai, India for generously sharing his laboratory facilities for fluorescence microscopy.
Publisher Copyright:
© 2014, Springer-Verlag Berlin Heidelberg.
PY - 2015/3
Y1 - 2015/3
N2 - Purpose: The deficiency of glutathione (GSH) has been linked to several diseases. The study investigated the role of GSH as a protective factor against hyperglycemia-mediated injury in VL-17A cells treated with 50 mM glucose. Methods: The cell viability and different oxidative stress parameters including glyoxalase I activity were measured. Results: GSH supplementation with 2 mM N-acetyl cysteine (NAC) or 0.1 mM ursodeoxycholic acid (UDCA) increased the viability, GSH level and the GSH-dependent glyoxalase I activity in 50 mM glucose-treated VL-17A cells. Further, pretreatment of 50 mM glucose-treated VL-17A cells with NAC or UDCA decreased oxidative stress (levels of reactive oxygen species and protein carbonylation), apoptosis (caspase 3 activity and annexin V–propidium iodide positive cells) and glutathionylated protein formation, a measure of oxidative stress. GSH depletion with 0.4 mM buthionine sulfoximine (BSO) or 1 mM diethyl maleate (DEM) potentiated the decrease in viability, glyoxalase I activity and increase in oxidative stress and apoptosis, with decreased GSH levels in 50 mM glucose-treated VL-17A cells. Conclusion: Thus, changes in GSH levels with exogenous agents such as NAC, UDCA, BSO or DEM modulate hyperglycemia-mediated injury in a cell model of VL-17A liver cells.
AB - Purpose: The deficiency of glutathione (GSH) has been linked to several diseases. The study investigated the role of GSH as a protective factor against hyperglycemia-mediated injury in VL-17A cells treated with 50 mM glucose. Methods: The cell viability and different oxidative stress parameters including glyoxalase I activity were measured. Results: GSH supplementation with 2 mM N-acetyl cysteine (NAC) or 0.1 mM ursodeoxycholic acid (UDCA) increased the viability, GSH level and the GSH-dependent glyoxalase I activity in 50 mM glucose-treated VL-17A cells. Further, pretreatment of 50 mM glucose-treated VL-17A cells with NAC or UDCA decreased oxidative stress (levels of reactive oxygen species and protein carbonylation), apoptosis (caspase 3 activity and annexin V–propidium iodide positive cells) and glutathionylated protein formation, a measure of oxidative stress. GSH depletion with 0.4 mM buthionine sulfoximine (BSO) or 1 mM diethyl maleate (DEM) potentiated the decrease in viability, glyoxalase I activity and increase in oxidative stress and apoptosis, with decreased GSH levels in 50 mM glucose-treated VL-17A cells. Conclusion: Thus, changes in GSH levels with exogenous agents such as NAC, UDCA, BSO or DEM modulate hyperglycemia-mediated injury in a cell model of VL-17A liver cells.
KW - Glutathione
KW - Hyperglycemia
KW - Injury
KW - Liver
KW - Reactive oxygen species
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U2 - 10.1007/s00394-014-0703-2
DO - 10.1007/s00394-014-0703-2
M3 - Article
C2 - 24756473
AN - SCOPUS:84939872032
SN - 1436-6207
VL - 54
SP - 223
EP - 234
JO - European Journal of Nutrition
JF - European Journal of Nutrition
IS - 2
ER -