Differential effects of cannabinoid receptor agonists GP1a and L-alpha-lysophosphatidylinositol on alcohol-induced reactive oxygen species
Department
Biological Sciences
Faculty Advisor
Marisela Agudelo
Start Date
1-10-2020 2:00 PM
End Date
1-10-2020 3:00 PM
Abstract
According to the National Institute on Alcohol Abuse and Alcoholism, in 2017, 14.1 million adults were labeled as having an Alcohol Abuse Disorder.[1] Recent studies have elucidated that alcohol abuse can lead to various forms of cellular injury, including DNA damage, lipid degradation, changes in protein structure, and even lead to the onset of several alcohol-related diseases through the dysregulation of reactive oxygen species (ROS) and antioxidant defense mechanisms .[2][3] In animal models, chronic alcohol feeding correlated with a heavy increase in inflammatory macrophage migration to the liver and severe tissue liver damage as a result of increased number of inflammatory mediators.[4] Furthermore, ROS are negatively-charged free radical byproducts of oxygen metabolism capable of causing much damage if not for the presence of antioxidants. Therefore, research strategies to modulate and reduce the effects of alcohol-induced ROS in order to prevent the development of alcohol-induced inflammation are of interest. Oxidative damage to dendritic cells has also been associated with aging and age-related degenerative diseases, as well as increased autoimmunity and hypomethylation of various genes.[5] In our lab, we have previously studied the effects of chronic alcohol exposure on monocyte-derived dendritic cells and tested to see if Trichostatin A, a histone modulator, had the ability to block or reverse the effects of chronic alcohol exposure.[6] One of the systems involved in alcohol-induced modulation and of interest in our lab is the endocannabinoid system for modulating neuropathic pain and treating inflammatory responses in the central and peripheral nervous system due to neuroimmune responses following injury or the onset of neurodegenerative diseases. The endocannabinoid system is a complex system found embedded throughout the central and peripheral nervous system of mammals composed of ligands, receptors, and enzymes that contribute to the body’s regulatory functions.[7] We induced the activation of the endocannabinoid system with L-α-lysophosphatidylinositol, a GPR55 agonist, and GP1a, a CB2 agonist. GP1a has shown to be an important moderator in neuroinflammatory responses following traumatic brain injury. Its activation decreases M1 macrophage polarization in favor of M2 anti-inflammatory macrophage polarization.[8] On the other hand, LPI has its ability to modulate synaptic activity through GPR55 activation.[9] The in-vitro alcohol treatment
File Type
Event
Differential effects of cannabinoid receptor agonists GP1a and L-alpha-lysophosphatidylinositol on alcohol-induced reactive oxygen species
According to the National Institute on Alcohol Abuse and Alcoholism, in 2017, 14.1 million adults were labeled as having an Alcohol Abuse Disorder.[1] Recent studies have elucidated that alcohol abuse can lead to various forms of cellular injury, including DNA damage, lipid degradation, changes in protein structure, and even lead to the onset of several alcohol-related diseases through the dysregulation of reactive oxygen species (ROS) and antioxidant defense mechanisms .[2][3] In animal models, chronic alcohol feeding correlated with a heavy increase in inflammatory macrophage migration to the liver and severe tissue liver damage as a result of increased number of inflammatory mediators.[4] Furthermore, ROS are negatively-charged free radical byproducts of oxygen metabolism capable of causing much damage if not for the presence of antioxidants. Therefore, research strategies to modulate and reduce the effects of alcohol-induced ROS in order to prevent the development of alcohol-induced inflammation are of interest. Oxidative damage to dendritic cells has also been associated with aging and age-related degenerative diseases, as well as increased autoimmunity and hypomethylation of various genes.[5] In our lab, we have previously studied the effects of chronic alcohol exposure on monocyte-derived dendritic cells and tested to see if Trichostatin A, a histone modulator, had the ability to block or reverse the effects of chronic alcohol exposure.[6] One of the systems involved in alcohol-induced modulation and of interest in our lab is the endocannabinoid system for modulating neuropathic pain and treating inflammatory responses in the central and peripheral nervous system due to neuroimmune responses following injury or the onset of neurodegenerative diseases. The endocannabinoid system is a complex system found embedded throughout the central and peripheral nervous system of mammals composed of ligands, receptors, and enzymes that contribute to the body’s regulatory functions.[7] We induced the activation of the endocannabinoid system with L-α-lysophosphatidylinositol, a GPR55 agonist, and GP1a, a CB2 agonist. GP1a has shown to be an important moderator in neuroinflammatory responses following traumatic brain injury. Its activation decreases M1 macrophage polarization in favor of M2 anti-inflammatory macrophage polarization.[8] On the other hand, LPI has its ability to modulate synaptic activity through GPR55 activation.[9] The in-vitro alcohol treatment