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Mouse hepatocytes lacking mGlu5 metabotropic glutamate receptors are less sensitive to hypoxic damage
Marianna Storto1, Giuseppe Battaglia, Roberto Gradini
1I.N.M. Neuromed, Pozzilli, Italy.
Abstract:
Endogenous activation of type-5 metabotropic glutamate receptors contributes to the development of hypoxia-induced liver cell injury. We have strengthened this hypothesis using glutamate mGlu5 receptor knockout mice. Hepatocytes isolated from knockout mice were less sensitive to hypoxic cell damage than hepatocytes from wild-type mice as assessed by lactate dehydrogenase release and formation of reactive oxygen species. The mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP) also protect hepatocytes against hypoxic damage.
Insights
Endogenous activation of type-5 metabotropic glutamate receptors (mGluR5) contributes to liver cell injury during hypoxia. Blocking mGluR5 protected liver cells from hypoxic damage, confirming its role in cell injury.
Area of Science:
- Neuroscience
- Hepatology
- Cellular Biology
Background:
- Endogenous activation of type-5 metabotropic glutamate receptors (mGluR5) is implicated in hypoxia-induced liver cell injury.
- Understanding the precise role of mGluR5 in hepatic response to hypoxia is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the contribution of mGluR5 to hypoxia-induced liver cell injury.
- To evaluate the protective effects of mGluR5 antagonism against hypoxic liver damage.
Main Methods:
- Utilized glutamate mGlu5 receptor knockout mice to assess cellular sensitivity to hypoxia.
- Isolated hepatocytes from knockout and wild-type mice for comparative analysis.
- Measured lactate dehydrogenase release and reactive oxygen species formation as indicators of cell damage.
- Administered the mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), to evaluate its protective effects.
Main Results:
- Hepatocytes from mGluR5 knockout mice exhibited reduced sensitivity to hypoxic cell damage compared to wild-type controls.
- Lactate dehydrogenase release was significantly lower in hepatocytes from knockout mice.
- Formation of reactive oxygen species was diminished in hepatocytes lacking mGluR5.
- Treatment with MPEP demonstrated a protective effect on hepatocytes against hypoxic injury.
Conclusions:
- Endogenous activation of mGluR5 plays a significant role in mediating hypoxia-induced liver cell injury.
- mGluR5 knockout or antagonism provides protection against hepatic damage under hypoxic conditions.
- Targeting mGluR5 presents a potential therapeutic avenue for managing liver injury associated with hypoxia.
