Divergent dimethylarginine dimethylaminohydrolase isoenzyme expression in the central nervous system

Kozlova, Alena A.; Ragavan, Vinitha N.; Jarzebska, Natalia; Lukianova, Iana Vadimovna; Bikmurzina, Anastasia E.; Rubets, Elena; Suzuki-Yamamoto, Toshiko; Kimoto, Masumi; Mangoni, Arduino A.; Gainetdinov, Raul R.; Weiss, Norbert; Bauer, Michael J.; Markov, Alexander G.; Rodionov, Roman N.; Bernhardt, Nadine

doi:10.21203/rs.3.rs-148653/v1

Cited by 2 publications

(2 citation statements)

References 36 publications

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“…This result seems contradictory to that of the present study. As reported previously, DDAH-1 is distributed in multiple cell types, including neurons, astrocyte cells, and vascular structures, while DDAH-2 is distributed exclusively in neurons [33]. As a result, DDAH-1 knockout might affect…”

Section: Discussionmentioning

confidence: 54%

Asymmetric Dimethylarginine Protects Neurons from Oxygen Glucose Deprivation Insult by Modulating Connexin-36 Expression

Fang

Chen

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Asymmetric dimethylarginine (ADMA) is a nonselective nitric oxide synthase inhibitor. ADMA is thought to inhibit the production of nitric oxide (NO) by neurons after oxygen-glucose deprivation (OGD). The gap junction protein Connexin-36 (cx-36) is involved in the pathophysiology of stroke. We investigated whether ADMA could protect neurons from OGD insults by regulating the expression of cx-36. Methods. Cultured rat cortical neuronal cells were used. Neurons were treated with OGD with or without ADMA pretreatment. The lactate dehydrogenase (LDH) release rate was used to assess neuronal injury. Intracellular NO levels were determined using 4-amino-5-methylamino-2 ′ ,7 ′ -difluorofluorescein diacetate. Western blotting was performed to detect cx-36 expression. Results. The LDH release rate increased in the supernatant of neurons after the OGD insult, whereas ADMA treatment reduced the LDH release rate. Intracellular NO levels increased following OGD treatment, and this increase was not inhibited by ADMA treatment. Expression of cx-36 was upregulated in neurons under OGD conditions, and treatment with ADMA downregulated the expression of cx-36. Conclusions. ADMA protects neurons from OGD insult, and cx-36 downregulation may be a possible pathway involved in ADMA-mediated neuronal protection.

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Section: Discussionmentioning

confidence: 54%

Asymmetric Dimethylarginine Protects Neurons from Oxygen Glucose Deprivation Insult by Modulating Connexin-36 Expression

Fang

Chen

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…DDAH2, as a dimethylarginine dimethylaminohydrolase, regulates the cellular concentrations of methylarginines and generates nitric oxide. It is associated with chronic kidney disease and preeclampsia 81,82 . PARP1 (poly(ADPribosyl)transferase) is a chromatin-associated enzyme that modifies various nuclear proteins and DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and antiviral innate immunity 83 .…”

Section: Proteins Identified In Ipscs/npcs Function In Plasma Pathwaysmentioning

confidence: 99%

Integration and comparison of multi-omics profiles of NGLY1 deficiency plasma and cellular models to identify clinically relevant molecular phenotypes

Chen

Wang

Shen

et al. 2021

Preprint

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NGLY1 (N-glycanase 1) deficiency is a rare congenital recessive disorder caused by a mutation in the NGLY1 gene, which encodes the cytosol enzyme N-glycanase 1. The NGLY1 protein catalyzes the first step in protein deglycosylation, a process prerequisite for the cytosolic degradation of misfolded glycoproteins. By performing and combining metabolomics and proteomics profiles, we showed that NGLY1 deficiency induced the activation of immune response, disturbed lipid metabolism, biogenic amine synthesis and glutathione metabolism. The discovery was further validated by profiling of patient-derived induced pluripotent stem cells (iPSCs) and differentiated neural progenitor cells (NPCs), which serve as a personalized cellular model of the disease. This study provides new insights into the NGLY1 deficiency pathology and demonstrates that the upregulation of immune response and downregulation of lipid metabolism appear to be important molecular phenotypes of NGLY1 deficiency, together with the dysregulation of amino acid metabolism, biogenic amine synthesis and diverse signaling pathways, likely causing broad downstream syndromes. Collectively, such valuable multi-omics profiles identified broad molecular associations of potential pathological mechanisms during the onset of NGLY1 deficiency and suggested potential therapeutic targets for researchers and clinicians.

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Divergent dimethylarginine dimethylaminohydrolase isoenzyme expression in the central nervous system

Cited by 2 publications

References 36 publications

Asymmetric Dimethylarginine Protects Neurons from Oxygen Glucose Deprivation Insult by Modulating Connexin-36 Expression

Asymmetric Dimethylarginine Protects Neurons from Oxygen Glucose Deprivation Insult by Modulating Connexin-36 Expression

Integration and comparison of multi-omics profiles of NGLY1 deficiency plasma and cellular models to identify clinically relevant molecular phenotypes

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