Abstract
The effect of glucose-dependent insulinotropic polypeptide (GIP) on cells under oxidative stress induced by glutamate, a neurotransmitter, and the underlying molecular mechanisms were assessed in the present study. We found that in the pre-treatment of HT-22 cells with glutamate in a dose-dependent manner, intracellular ROS were excessively generated, and additional cell damage occurred in the form of lipid peroxidation. The neurotoxicity caused by excessive glutamate was found to be ferroptosis and not apoptosis. Other factors (GPx-4, Nrf2, Nox1 and Hspb1) involved in ferroptosis were also identified. In other words, it was confirmed that GIP increased the activity of sub-signalling molecules in the process of suppressing ferroptosis as an antioxidant and maintained a stable cell cycle even under glutamate-induced neurotoxicity. At the same time, in HT-22 cells exposed to ferroptosis as a result of excessive glutamate accumulation, GIP sustained cell viability by activating the mitogen-activated protein kinase (MAPK) signalling pathway. These results suggest that the overexpression of the GIP gene increases cell viability by regulating mechanisms related to cytotoxicity and reactive oxygen species production in hippocampal neuronal cell lines.
Highlights
We found that the type of programmed cell death caused by excessive glutamate-induced neurotoxicity in mouse hippocampal HT-22 cells is ferroptosis and
We found that the type of programmed cell death caused by excessive glutamate-induced neurotoxicity in mouse hippocampal HT-22 cells is ferroptosis and no apoptosis or parthanatos
The neuroprotective role of glucose-dependent insulinotropic polypeptide (GIP) was evident in the form of a normal cell cycle without any phase arrest and reactive oxygen species (ROS)-scavenging effects in the not apoptosis or parthanatos
Summary
Monosodium glutamate (MSG), the sodium salt of the non-essential amino acid, glutamic acid, is a well-known food flavour enhancer that is naturally present in many foods, including tomato, cheese, and meat [1]. MSG consumption has increased globally, excessive MSG intake has been associated with an increased risk of various diseases, such as obesity, diabetes and asthma [2]. The negative effects of MSG were revealed to the public due to Chinese restaurant syndrome, characterised by headache, throbbing of the head, dizziness, facial pressure, burning or tingling sensations over parts of the body and back pain [3]. Glutamate is the main excitatory neurotransmitter in the Antioxidants 2022, 11, 189.
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