The oncogenic lysophosphatidylinositol (LPI)/GPR55 signaling

Calvillo-Robledo, Argelia; Cervantes‐Villagrana, Rodolfo Daniel; Morales, Paula; Marichal‐Cancino, Bruno A.

doi:10.1016/j.lfs.2022.120596

Cited by 10 publications

(6 citation statements)

References 112 publications

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“…The activation of GPR55 by LPI leads to increased cell proliferation; therefore, if an increased expression level of this protein is detected in tumors, this is considered a marker of a poor prognosis for the development of the disease [ 10 , 11 ]. In addition, GPR55 is also involved in other processes.…”

Section: Introductionmentioning

confidence: 99%

The Mechanisms of GPR55 Receptor Functional Selectivity during Apoptosis and Proliferation Regulation in Cancer Cells

Akimov

Gretskaya

Dudina

et al. 2023

IJMS

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GPR55 is a non-canonical cannabinoid receptor, important for cancer proliferation. Depending on the ligand, it induces either cell proliferation or death. The objective of the study was to establish the mechanisms of this multidirectional signaling. Using the CRISPR-Cas9 system, the GPR55, CB1, CB2, and GPR18 receptor knockouts of the MDA-MB-231 line were obtained. After the CB2 receptor knockout, the pro-apoptotic activity of the pro-apoptotic ligand docosahexaenoyl dopamine (DHA-DA) slightly increased, while the pro-proliferative activity of the most active synthetic ligand of the GPR55 receptor (ML-184) completely disappeared. On the original cell line, the stimulatory effect of ML-184 was removed by the CB2 receptor blocker and by GPR55 receptor knockout. Thus, it can be confidently assumed that when proliferation is stimulated with the participation of the GPR55 receptor, a signal is transmitted from the CB2 receptor to the GPR55 receptor due to the formation of a heterodimer. GPR18 was additionally involved in the implementation of the pro-apoptotic effect of DHA-DA, while the CB1 receptor is not involved. In the implementation of the pro-apoptotic action of DHA-DA, the elimination of Gα13 led to a decrease in cytotoxicity. The obtained data provide novel details to the mechanism of the pro-proliferative action of GPR55.

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Section: Introductionmentioning

confidence: 99%

The Mechanisms of GPR55 Receptor Functional Selectivity during Apoptosis and Proliferation Regulation in Cancer Cells

Akimov

Gretskaya

Dudina

et al. 2023

IJMS

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“…G-protein-coupled receptor 55 (GPR55), an orphan class A G protein-coupled receptor identified in 1999 11 , recognizes multiple ligands and is associated with many physiological and pathophysiological processes that affect the central nervous system, cardiovascular system, bone remodeling, immune system control, gastrointestinal and metabolic function, and adipose tissue control 11 . In a mouse model of enteritis, GPR55-deficient mice displayed reduced levels of inflammation and macrophage infiltration 12 .…”

Section: Introductionmentioning

confidence: 99%

Lysophosphatidylglucoside/GPR55 signaling promotes foam cell formation in human M2c macrophages

Shimai,

Hanafusa,

Nakayama

et al. 2023

Sci Rep

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Atherosclerosis is a major cause of cerebral and cardiovascular diseases. Intravascular plaques, a well-known pathological finding of atherosclerosis, have a necrotic core composed of macrophages and dead cells. Intraplaque macrophages, which are classified into various subtypes, play key roles in maintenance of normal cellular microenvironment. Excessive uptake of oxidized low-density lipoprotein causes conversion of macrophages to foam cells, and consequent progression/exacerbation of atherosclerosis. G-protein-coupled receptor 55 (GPR55) signaling has been reported to associate with atherosclerosis progression. We demonstrated recently that lysophosphatidylglucoside (lysoPtdGlc) is a specific ligand of GPR55, although in general physiological ligands of GPR55 are poorly understood. Phosphatidylglucoside is expressed on human monocytes and can be converted to lysoPtdGlc. In the present study, we examined possible involvement of lysoPtdGlc/GPR55 signaling in foam cell formation. In monocyte-derived M2c macrophages, lysoPtdGlc/GPR55 signaling inhibited translocation of ATP binding cassette subfamily A member 1 to plasma membrane, and cholesterol efflux. Such inhibitory effect was reversed by GPR55 antagonist ML193. LysoPtdGlc/GPR55 signaling in M2c macrophages was involved in excessive lipid accumulation, thereby promoting foam cell formation. Our findings suggest that lysoPtdGlc/GPR55 signaling is a potential therapeutic target for inhibition of atherosclerosis progression.

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“…Another minor component of the cell membrane, LPE, is involved in the activation of enzymes and the mediation of cell signaling, and alterations in its expression in a mouse model of mTBI paralleled those detected in soldiers that had endured chronic mTBI ( Emmerich et al, 2017 ), but alterations may be region-specific and time-sensitive ( Ojo et al, 2018 ). LPI is a bioactive lipid that targets the GRP55 endocannabinoid receptor and influences cell growth, differentiation, and motility in various cell types ( Calvillo-Robledo et al, 2022 ), and it was shown to be protective against glutamate-induced excitotoxicity ( Blondeau et al, 2002 ). However, few research endeavours have evaluated the trajectory of lipid alterations after single and repeated mTBIs, and the relationship between lipid abnormalities and other pathological characteristics of mTBI, such as neurometabolic and mitochondrial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Acute effects of single and repeated mild traumatic brain injury on levels of neurometabolites, lipids, and mitochondrial function in male rats

Allen

Pham

Bond

et al. 2023

Front. Mol. Neurosci.

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IntroductionMild traumatic brain injuries (mTBIs) are the most common form of acquired brain injury. Symptoms of mTBI are thought to be associated with a neuropathological cascade, potentially involving the dysregulation of neurometabolites, lipids, and mitochondrial bioenergetics. Such alterations may play a role in the period of enhanced vulnerability that occurs after mTBI, such that a second mTBI will exacerbate neuropathology. However, it is unclear whether mTBI-induced alterations in neurometabolites and lipids that are involved in energy metabolism and other important cellular functions are exacerbated by repeat mTBI, and if such alterations are associated with mitochondrial dysfunction.MethodsIn this experiment, using a well-established awake-closed head injury (ACHI) paradigm to model mTBI, male rats were subjected to a single injury, or five injuries delivered 1 day apart, and injuries were confirmed with a beam-walk task and a video observation protocol. Abundance of several neurometabolites was evaluated 24 h post-final injury in the ipsilateral and contralateral hippocampus using in vivo proton magnetic resonance spectroscopy (1H-MRS), and mitochondrial bioenergetics were evaluated 30 h post-final injury, or at 24 h in place of 1H-MRS, in the rostral half of the ipsilateral hippocampus. Lipidomic evaluations were conducted in the ipsilateral hippocampus and cortex.ResultsWe found that behavioral deficits in the beam task persisted 1- and 4 h after the final injury in rats that received repetitive mTBIs, and this was paralleled by an increase and decrease in hippocampal glutamine and glucose, respectively, whereas a single mTBI had no effect on sensorimotor and metabolic measurements. No group differences were observed in lipid levels and mitochondrial bioenergetics in the hippocampus, although some lipids were altered in the cortex after repeated mTBI.DiscussionThe decrease in performance in sensorimotor tests and the presence of more neurometabolic and lipidomic abnormalities, after repeated but not singular mTBI, indicates that multiple concussions in short succession can have cumulative effects. Further preclinical research efforts are required to understand the underlying mechanisms that drive these alterations to establish biomarkers and inform treatment strategies to improve patient outcomes.

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The oncogenic lysophosphatidylinositol (LPI)/GPR55 signaling

Cited by 10 publications

References 112 publications

The Mechanisms of GPR55 Receptor Functional Selectivity during Apoptosis and Proliferation Regulation in Cancer Cells

The Mechanisms of GPR55 Receptor Functional Selectivity during Apoptosis and Proliferation Regulation in Cancer Cells

Lysophosphatidylglucoside/GPR55 signaling promotes foam cell formation in human M2c macrophages

Acute effects of single and repeated mild traumatic brain injury on levels of neurometabolites, lipids, and mitochondrial function in male rats

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