Decrease in gamma-glutamyltransferase activity in rat type II cells exposed in vitro to hyperoxia: effects of the...

Area of Science:

• Biochemistry
• Cell Biology
• Pulmonary Medicine

Background:

• Hyperoxia is known to affect antioxidant enzymes.
• The impact of subtoxic hyperoxia on gamma-glutamyltransferase (gamma-GT), crucial for glutathione (GSH) synthesis, remains unclear.
• Gamma-GT plays a role in extracellular GSH uptake and intracellular synthesis.

Purpose of the Study:

• To investigate the in vitro effects of hyperoxia on rat type II cell gamma-GT activity.
• To evaluate the protective effects of lazaroid U-74389G and N-acetylcysteine (NAC) on hyperoxia-induced changes in gamma-GT and antioxidant enzymes.

Main Methods:

• Rat type II cells were exposed to air, 60% O2, or 85% O2 for 2 days.
• Cells were treated with or without U-74389G or NAC.
• Assays included gamma-GT activity, GSH levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity.
• Northern blotting was used to assess gamma-GT mRNA levels.

Main Results:

• Hyperoxia (60% and 85% O2) significantly decreased gamma-GT activity and intracellular GSH levels.
• Antioxidant enzymes SOD and GPx activities increased under 85% O2 exposure.
• U-74389G treatment prevented the hyperoxia-induced decrease in gamma-GT and GSH.
• NAC treatment increased GSH levels but did not restore gamma-GT activity.
• Gamma-GT mRNA levels were unaffected by hyperoxia.

Conclusions:

• Hyperoxia in vitro decreases gamma-GT activity in rat type II cells.
• This effect is likely due to direct inactivation of membrane-bound gamma-GT, not transcriptional regulation or altered GSH levels.
• The lazaroid U-74389G demonstrates a protective effect against hyperoxia-induced gamma-GT reduction.