Glutathione S-Transferases (GSTs) are a family of enzymes involved in the detoxification of endogenous and exogenous compounds. They catalyze the conjugation of the reduced form of glutathione (GSH) to xenobiotic substrates, facilitating their excretion from the body . Among the various classes of GSTs, the Pi class (GSTP) is particularly noteworthy due to its abundance and functional significance in mammalian cells .
GSTP is a homodimeric enzyme, meaning it consists of two identical subunits. Each subunit has a GSH-binding site and a substrate-binding site (H-site), which together facilitate the enzyme’s catalytic activity . The enzyme’s primary function is to detoxify harmful compounds by conjugating them with GSH, making them more water-soluble and easier to excrete .
In mice, the GSTP gene cluster includes multiple isoforms, with GSTP2 being one of the prominent ones. Mouse recombinant GSTP2 is often used in research to study the enzyme’s role in various physiological and pathological processes. The recombinant form is produced by cloning the GSTP2 gene into an expression vector, which is then introduced into a host cell (usually bacteria) to produce the enzyme in large quantities.
GSTP2 plays a crucial role in detoxifying a wide range of harmful compounds, including carcinogens, environmental toxins, and products of oxidative stress . It has been shown to protect cells from damage induced by these compounds, thereby reducing the risk of diseases such as cancer and liver toxicity .
Recent studies have highlighted the role of GSTP in modulating inflammatory responses. For instance, GSTP has been shown to play an anti-inflammatory role in macrophages, suggesting that it may have a protective role in inflammation . In a study involving experimental sepsis, deletion of the murine Gstp gene cluster significantly decreased mortality and reduced serum levels of high mobility group box-1 protein (HMGB1), a key cytokine involved in septic death . This indicates that GSTP may help prevent the translocation and release of HMGB1, thereby mitigating the severity of sepsis .
To better understand the role of GSTP in human physiology, researchers have developed mouse models that express human GSTP1. These models have provided valuable insights into the enzyme’s role in liver toxicity and drug metabolism . For example, mice expressing human GSTP1 showed different patterns of enzyme regulation and response to acetaminophen overdose compared to wild-type mice . This suggests that GSTP may be a critical determinant of toxin-induced hepatocyte injury, even when not expressed by hepatocytes .