Involvement of Metabolic Lipid Mediators in the Regulation of Apoptosis

Abstract

Apoptosis is the physiological mechanism of cell death and can be modulated by endogenous and exogenous factors, including stress and metabolic alterations. Reactive oxygen species (ROS), as well as ROS-dependent lipid peroxidation products (including isoprostanes and reactive aldehydes including 4-hydroxynonenal) are proapoptotic factors. These mediators can activate apoptosis via mitochondrial-, receptor-, or ER stress-dependent pathways. Phospholipid metabolism is also an essential regulator of apoptosis, producing the proapoptotic prostaglandins of the PGD and PGJ series, as well as the antiapoptotic prostaglandins of the PGE series, but also 12-HETE and 20-HETE. The effect of endocannabinoids and phytocannabinoids on apoptosis depends on cell type-specific differences. Cells where cannabinoid receptor type 1 (CB1) is the dominant cannabinoid receptor, as well as cells with high cyclooxygenase (COX) activity, undergo apoptosis after the administration of cannabinoids. In contrast, in cells where CB2 receptors dominate, and cells with low COX activity, cannabinoids act in a cytoprotective manner. Therefore, cell type-specific differences in the pro- and antiapoptotic effects of lipids and their (oxidative) products might reveal new options for differential bioanalysis between normal, functional, and degenerating or malignant cells, and better integrative biomedical treatments of major stress-associated diseases.

Cannabidiol Modifies the Formation of NETs in Neutrophils of Psoriatic Patients

“…Oxidative stress also promotes other metabolic changes, including an increase in the production of pro-inflammatory cytokines, which we and other authors previously observed in granulocytes of patients with psoriasis [ 8 , 29 , 30 ]. In addition, ROS can react with lipids, proteins and nucleic acids to modify their structure and functions, and has been observed with proteins and lipids in psoriatic blood cells [ 7 , 8 , 29 , 31 ]. This type of action is believed to lead to the exacerbation of disease symptoms [ 8 ].…”

Quantitative Profiling of Oxylipins in Acute Experimental Intracerebral Hemorrhage

“…VIP values were calculated by an OPLS-DA model using the metaboanalyst software. (Sudhahar et al, 2010;Bennett and Gilroy, 2016;Figueiredo-Pereira et al, 2016;Shearer and Walker, 2018;Rahman et al, 2019;Wójcik et al, 2020). Of note, these oxylipins of AA change with the progression of ICH and the destructive oxylipins appear to peak 3 days after ICH when the protective oxylipins of AA have descended suggesting that AA-derived oxylipins tend to cause damage with the development of ICH.…”

“…Compared to oxylipins derived from n–3 PUFAs (DHA, EPA), those derived from n–6 PUFAs (AA, LA) generally, but not always, exhibit pro-inflammatory, vasoconstrictive, and proliferative effects ( Gabbs et al, 2015 ). In the acute phase of ICH, the increased production of LTE4, PGJ2, 5-oxo-ETE, and 15-oxo-ETE derived from AA may exhibit vasoconstrictive, pro-apoptotic, pro-inflammatory, and chemoattractant effects which are inclined to aggregate the damage of ICH, while 5,6-DiHETrE, 12-HETE, and EETs show opposing effects such as vasodilative, anti-apoptotic, or anti-inflammatory activities ( Sudhahar et al, 2010 ; Bennett and Gilroy, 2016 ; Figueiredo-Pereira et al, 2016 ; Shearer and Walker, 2018 ; Rahman et al, 2019 ; Wójcik et al, 2020 ). Of note, these oxylipins of AA change with the progression of ICH and the destructive oxylipins appear to peak 3 days after ICH when the protective oxylipins of AA have descended suggesting that AA-derived oxylipins tend to cause damage with the development of ICH.…”

Cannabidiol-Mediated Changes to the Phospholipid Profile of UVB-Irradiated Keratinocytes from Psoriatic Patients

“…This is important for the recognition of apoptotic cells by macrophages and their subsequent removal by phagocytosis [44]. Phospholipid metabolism is also an essential regulator of apoptosis, a highly desirable event in psoriasis to prevent the hyperproliferation of keratinocytes [45]. The process of phospholipid transformation catalyzed by cyclooxygenase and lipoxygenase leads to the generation of D-series prostaglandins and J-series prostaglandins.…”

“…These mediators, through various metabolic pathways, induce apoptosis of keratinocytes [46]. Moreover, ROS-dependent lipid peroxidation end products, namely 4-HNE and 4-HHE, also induce apoptosis through their involvement in the receptor pathway of apoptosis [45].…”