Phenotypic Characterization of the Endocannabinoid-Degrading Enzyme Alpha/Beta-Hydrolase Domain 6 Knockout Rat

Noguchi, Katsuhiko; Kadekawa, Katsumi; Nishijima, Saori; Sakanashi, Mayuko; Okitsu-Sakurayama, Shiho; Higa‐Nakamine, Sayomi; Yamamoto, Hideyuki; Sugaya, Kimio

doi:10.1089/can.2021.0011

Cited by 6 publications

(3 citation statements)

References 28 publications

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“…ABHD6 is a newly discovered post‐genomic protein and was identified as a bona fide member of the endocannabinoid signaling system 11,12 . Until now, some studies have focused on the role and potential therapeutic target of ABHD6 in demyelinating disease, 13,14 inflammatory processes, 15 physiological processes, 16,17 and even the regulation of bladder function 18 . However, the role of ABHD6 in tumors, unlike MAGL, remains controversial and was found differentially expressed among various tumor cell lines 19 .…”

Section: Introductionmentioning

confidence: 99%

“…11,12 Until now, some studies have focused on the role and potential therapeutic target of ABHD6 in demyelinating disease, 13,14 inflammatory processes, 15 physiological processes, 16,17 and even the regulation of bladder function. 18 However, the role of ABHD6 in tumors, unlike MAGL, remains controversial and was found differentially expressed among various tumor cell lines. 19 It is reported that ABHD6 is highly expressed in Ewing family tumors (EFT) but knockdown of it did not inhibit the growth of EFT cells.…”

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confidence: 99%

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ABHD6 suppresses colorectal cancer progression via AKT signaling pathway

Xiong,

Yang,

Jin

et al. 2024

Molecular Carcinogenesis

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Colorectal cancer (CRC) continues to be a prevalent malignancy, posing a significant risk to human health. The involvement of alpha/beta hydrolase domain 6 (ABHD6), a serine hydrolase family member, in CRC development was suggested by our analysis of clinical data. However, the role of ABHD6 in CRC remains unclear. This study seeks to elucidate the clinical relevance, biological function, and potential molecular mechanisms of ABHD6 in CRC. We investigated the role of ABHD6 in clinical settings, conducting proliferation, migration, and cell cycle assays. To determine the influence of ABHD6 expression levels on Oxaliplatin sensitivity, we also performed apoptosis assays. RNA sequencing and KEGG analysis were utilized to uncover the potential molecular mechanisms of ABHD6. Furthermore, we validated its expression levels using Western blot and reactive oxygen species (ROS) detection assays. Our results demonstrated that ABHD6 expression in CRC tissues was notably lower compared to adjacent normal tissues. This low expression correlated with a poorer prognosis for CRC patients. Moreover, ABHD6 overexpression impeded CRC cell proliferation and migration while inducing G0/G1 cell cycle arrest. In vivo experiments revealed that downregulation of ABHD6 resulted in an increase in tumor weight and volume. Mechanistically, ABHD6 overexpression inhibited the activation of the AKT signaling pathway and decreased ROS levels in CRC cells, suggesting the role of ABHD6 in CRC progression via the AKT signaling pathway. Our findings demonstrate that ABHD6 functions as a tumor suppressor, primarily by inhibiting the AKT signaling pathway. This role establishes ABHD6 as a promising prognostic biomarker and a potential therapeutic target for CRC patients.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

ABHD6 suppresses colorectal cancer progression via AKT signaling pathway

Xiong,

Yang,

Jin

et al. 2024

Molecular Carcinogenesis

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“…α/β-Hydrolase domain-containing 6 (ABHD6) is an integral membrane protein with recently discovered serine hydrolase activity that is, mainly expressed in immune cell-enriched tissues and the CNS( Poursharifi et al, 2017 ). The hydrolytic substrates of ABHD6 are mainly monoacylglycerols (MAGs) ( Poursharifi et al, 2020 ), such as endogenous cannabinoid 2-arachidonoylglycerol (2-AG) and arachidonic acid ( Noguchi et al, 2021 ), which are precursors of prostaglandins and other inflammatory mediators ( Ghosh et al, 2020 ; Larsson et al, 2021 ; Trostchansky et al, 2021 ). As the main hydrolase of postsynaptic eCBs, ABHD6 is involved in regulating neuronal ECS function ( Cao et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Alpha/Beta-Hydrolase Domain-Containing 6: Signaling and Function in the Central Nervous System

Zhang

Liú

et al. 2021

Front. Pharmacol.

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Endocannabinoid (eCB) signaling plays an important role in the central nervous system (CNS). α/β-Hydrolase domain-containing 6 (ABHD6) is a transmembrane serine hydrolase that hydrolyzes monoacylglycerol (MAG) lipids such as endocannabinoid 2-arachidonoyl glycerol (2-AG). ABHD6 participates in neurotransmission, inflammation, brain energy metabolism, tumorigenesis and other biological processes and is a potential therapeutic target for various neurological diseases, such as traumatic brain injury (TBI), multiple sclerosis (MS), epilepsy, mental illness, and pain. This review summarizes the molecular mechanisms of action and biological functions of ABHD6, particularly its mechanism of action in the pathogenesis of neurological diseases, and provides a theoretical basis for new pharmacological interventions via targeting of ABHD6.

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Analgesic Properties of Next-Generation Modulators of Endocannabinoid Signaling: Leveraging Modern Tools for the Development of Novel Therapeutics

Singh,

Ellioff,

Bruchas

et al. 2024

J Pharmacol Exp Ther

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Targeting the endocannabinoid (eCB) signaling system for pain relief is an important treatment option that is only now beginning to be mechanistically explored. In this review, we focus on two recently appreciated cannabinoid-based targeting strategies, treatments with cannabidiol (CBD) and -hydrolase domain containing 6 (ABHD6) inhibitors, which have the exciting potential to produce pain relief through distinct mechanisms of action (MOA) and without intoxication. We review evidence on plantderived cannabinoids for pain, with an emphasis on CBD and its multiple molecular targets expressed in pain pathways. We also discuss the function of eCB signaling in regulating pain responses and the therapeutic promises of inhibitors targeting ABHD6, a 2-arachidonoylglycerol (2-AG) hydrolyzing enzyme. Finally, we discuss how the novel cannabinoid biosensor, GRAB eCB2.0 , may be leveraged to enable the discovery of targets modulated by cannabinoids at a circuit-specific level. Significance StatementCannabis has been used by humans as an effective medicine for millennia, including for pain management. Recent evidence emphasizes the therapeutic potential of compounds that modulate endocannabinoid signaling. Specifically, cannabidiol and inhibitors of the enzyme ABHD6 represent promising strategies to achieve pain relief by modulating endocannabinoid signaling in pain pathways via distinct, non-intoxicating, mechanisms of action.

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Phenotypic Characterization of the Endocannabinoid-Degrading Enzyme Alpha/Beta-Hydrolase Domain 6 Knockout Rat

Cited by 6 publications

References 28 publications

ABHD6 suppresses colorectal cancer progression via AKT signaling pathway

ABHD6 suppresses colorectal cancer progression via AKT signaling pathway

Alpha/Beta-Hydrolase Domain-Containing 6: Signaling and Function in the Central Nervous System

Analgesic Properties of Next-Generation Modulators of Endocannabinoid Signaling: Leveraging Modern Tools for the Development of Novel Therapeutics

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