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Neurobiology of Disease May 2024Emerging evidence has implicated an important role of synapse-associated protein-97 (SAP97)-regulated GluA1-containing AMPARs membrane trafficking in cocaine restate and...
Spinal nerve transection-induced upregulation of SAP97 via promoting membrane trafficking of GluA1-containing AMPA receptors in the dorsal horn contributes to the pathogenesis of neuropathic pain.
Emerging evidence has implicated an important role of synapse-associated protein-97 (SAP97)-regulated GluA1-containing AMPARs membrane trafficking in cocaine restate and in contextual episodic memory of schizophrenia. Herein, we investigated the role of SAP97 in neuropathic pain following lumbar 5 spinal nerve transection (SNT) in rats. Our results showed that SNT led to upregulation of SAP97, enhanced the interaction between SAP97 and GluA1, and increased GluA1-containing AMPARs membrane trafficking in the dorsal horn. Microinjection of AAV-EGFP-SAP97 shRNA in lumbar 5 spinal dorsal horn inhibited SAP97 production, decreased SAP97-GluA1 interaction, reduced the membrane trafficking of GluA1-containing AMPARs, and partially attenuated neuropathic pain following SNT. Intrathecal injections of SAP97 siRNA or NASPM, an antagonist of GluA1-containing AMPARs, also partially reversed neuropathic pain on day 7, but not on day 14, after SNT. Spinal overexpression of SAP97 by AAV-EGFP-SAP97 enhanced SAP97-GluA1 interaction, increased the membrane insertion of GluA1-containing AMPARs, and induced abnormal pain in naïve rats. In addition, treatment with SAP97 siRNA or NASPM i.t. injection alleviated SNT-induced allodynia and hyperalgesia and exhibited a longer effect in female rats. Together, our results indicate that the SNT-induced upregulation of SAP97 via promoting GluA1-containing AMPARs membrane trafficking in the dorsal horn contributes to the pathogenesis of neuropathic pain. Targeting spinal SAP97 might be a promising therapeutic strategy to treatment of chronic pain.
Topics: Animals; Female; Rats; Hyperalgesia; Neuralgia; Rats, Sprague-Dawley; Receptors, AMPA; RNA, Small Interfering; Spermine; Spinal Cord Dorsal Horn; Spinal Nerves; Up-Regulation
PubMed: 38461868
DOI: 10.1016/j.nbd.2024.106471 -
Scientific Reports Mar 2024Autism spectrum disorder (ASD) is a complicated, lifelong neurodevelopmental disorder affecting verbal and non-verbal communication and social interactions. ASD signs...
Autism spectrum disorder (ASD) is a complicated, lifelong neurodevelopmental disorder affecting verbal and non-verbal communication and social interactions. ASD signs and symptoms appear early in development before the age of 3 years. It is unlikely for a person to acquire autism after a period of normal development. However, we encountered an 8-year-old child who developed ASD later in life although his developmental milestones were normal at the beginning of life. Sequencing the complete coding part of the genome identified a hemizygous nonsense mutation (NM_001367857.2):c.1803C>G; (p.Tyr601Ter) in the gene (SATL1) encoding spermidine/spermine N1-acetyl transferase like 1. Screening an ASD cohort of 28 isolated patients for the SATL1 gene identified another patient with the same variant. Although SATL1 mutations have not been associated with any human diseases, our data suggests that a mutation in SATL1 is the underlying cause of ASD in our cases. In mammals, mutations in spermine synthase (SMS), an enzyme needed for the synthesis of spermidine polyamine, have been reported in a syndromic form of the X-linked mental retardation. Moreover, SATL1 gene expression studies showed a relatively higher expression of SATL1 transcripts in ASD related parts of the brain including the cerebellum, amygdala and frontal cortex. Additionally, spermidine has been characterized in the context of learning and memory and supplementations with spermidine increase neuroprotective effects and decrease age-induced memory impairment. Furthermore, spermidine biosynthesis is required for spontaneous axonal regeneration and prevents α-synuclein neurotoxicity in invertebrate models. Thus, we report, for the first time, that a mutation in the SATL1 gene could be a contributing factor in the development of autistic symptoms in our patients.
Topics: Animals; Child; Humans; Autism Spectrum Disorder; Polyamines; Spermidine; Spermine; Transferases
PubMed: 38459140
DOI: 10.1038/s41598-024-56253-5 -
Brazilian Journal of Biology = Revista... 2024The production of seedlings of the passion fruit tree, usually, is sexual, and the seeds are not uniform in the seedling emergence, and soaking treatments of seeds can...
The production of seedlings of the passion fruit tree, usually, is sexual, and the seeds are not uniform in the seedling emergence, and soaking treatments of seeds can provide faster and more uniform germination. It was aimed to study the action of plant growth regulators and the mobilization of reserves in the stages of soaking of yellow passion fruit seeds. The seeds were soaked for five hours in solutions containing plant growth regulators, in a completely randomized design, in a factorial 8 x 4, with four replications. The first factor corresponds to eight plant growth regulators: T1 - distilled water (control); T2 - 6-benzylaminepurine 500 mg L-1; T3 - 4-(3-indolyl) butyric acid 500 mg L-1; T4 - gibberellic acid 500 mg L-1; T5 - spermine 250 mg L-1; T6 - spermine 750 mg L-1; T7 - spermidine 750 mg L-1; T8 - spermidine 1250 mg L-1; and the second factor, to the four soaking times: zero, four, 72 and 120 hours, corresponding, respectively, to the dry seed, and to phases I, II, and III of the imbibition curve. It was evaluated the biochemical composition of seeds (lipids, soluble sugars and starch). The seeds showed accumulation of lipids in phase III; the content of soluble sugars increased in phase I and decreased in phase II. The starch content increased until the phase II and decreased in phase III. Starch is the main reserve in the seeds and the main source of energy used in phase III; soaking the seeds in polyamines generates an accumulation of lipids in the seeds and soaking in plant growth regulators increases the burning of starch.
Topics: Plant Growth Regulators; Passiflora; Fruit; Spermidine; Spermine; Butyric Acid; Seedlings; Starch; Sugars
PubMed: 38451628
DOI: 10.1590/1519-6984.273999 -
Frontiers in Microbiology 2024Engineering for biodegradation and transformation of industrial toxic substances such as catechol (CA) has received widespread attention, but the low tolerance of to...
Engineering for biodegradation and transformation of industrial toxic substances such as catechol (CA) has received widespread attention, but the low tolerance of to CA has limited its development. The exploration and modification of genes or pathways related to CA tolerance in is an effective way to further improve the utilization efficiency of CA. This study identified 36 genes associated with CA tolerance in through genome-wide identification and bioinformatics analysis and the knockout strain (Δ) is the most sensitive to CA. Based on the omics analysis of Δ under CA stress, it was found that knockout affects pathways such as intrinsic component of membrane and pentose phosphate pathway. In addition, the study revealed that 29 genes related to the cell wall-membrane system were up-regulated by more than twice, NADPH and NADP were increased by 2.48 and 4.41 times respectively, and spermidine and spermine were increased by 2.85 and 2.14 times, respectively, in Δ. Overall, the response of cell wall-membrane system, the accumulation of spermidine and NADPH, as well as the increased levels of metabolites in pentose phosphate pathway are important findings in improving the CA resistance. This study provides a theoretical basis for improving the tolerance of strains to CA and reducing the damage caused by CA to the ecological environment and human health.
PubMed: 38450166
DOI: 10.3389/fmicb.2024.1364425 -
Bone & Joint Research Mar 2024Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies,...
AIMS
Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear.
METHODS
In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression.
RESULTS
The results showed that inhibition of Sat1 expression can reduce inflammation, ferroptosis changes, reactive oxygen species (ROS) level, and lipid-ROS accumulation induced by IL-1β and Erastin. Knockdown of Sat1 promotes nuclear factor-E2-related factor 2 (Nrf2) signalling. Additionally, knockdown Alox15 can alleviate the inflammation-related protein expression induced by IL-1β and ferroptosis-related protein expression induced by Erastin. Furthermore, knockdown Nrf2 can reverse these protein expression alterations. Finally, intra-articular injection of diminazene aceturate (DA), an inhibitor of Sat1, enhanced type II collagen (collagen II) and increased Sat1 and Alox15 expression.
CONCLUSION
Our results demonstrate that inhibition of Sat1 could alleviate chondrocyte ferroptosis and inflammation by downregulating Alox15 activating the Nrf2 system, and delaying the progression of OA. These findings suggest that Sat1 provides a new approach for studying and treating OA.
PubMed: 38447596
DOI: 10.1302/2046-3758.133.BJR-2023-0250.R1 -
Journal of Agricultural and Food... Mar 2024Polyamines and their derivatives are ubiquitously present in free or conjugated forms in various foods from animal, plant, and microbial origins. The current knowledge... (Review)
Review
Polyamines and their derivatives are ubiquitously present in free or conjugated forms in various foods from animal, plant, and microbial origins. The current knowledge of free polyamines in foods and their contents is readily available; furthermore, conjugated polyamines generate considerable recent research interest due to their potential health benefits. The structural diversity of conjugated polyamines results in challenging their qualitative and quantitative analysis in food. Herein, we review and summarize the knowledge published on polyamines and their derivatives in foods, including their identification, sources, quantities, and health benefits. Particularly, facing the inherent challenges of isomer identification in conjugated polyamines, this paper provides a comprehensive overview of conjugated polyamines' structural characteristics, including the cleavage patterns and characteristic ion fragments of MS/MS for isomer identification. Free polyamines are present in all types of food, while conjugated polyamines are limited to plant-derived foods. Spermidine is renowned for antiaging properties, acclaimed as antiaging vitamins. Conjugated polyamines highlight their anti-inflammatory properties and have emerged as the mainstream drugs for antiprostatitis. This paper will likely help us gain better insight into polyamines and their derivatives to further develop functional foods and personalized nutraceuticals.
Topics: Animals; Polyamines; Tandem Mass Spectrometry; Spermidine; Plants; Spermine
PubMed: 38416110
DOI: 10.1021/acs.jafc.3c08556 -
Scientific Reports Feb 2024Intestinal adaptation does not necessarily recover absorptive capacity in short bowel syndrome (SBS), sometimes resulting in intestinal failure-associated liver disease...
Intestinal adaptation does not necessarily recover absorptive capacity in short bowel syndrome (SBS), sometimes resulting in intestinal failure-associated liver disease (IFALD). Additionally, its therapeutic options remain limited. Polyamines (spermidine and spermine) are known as one of the autophagy inducers and play important roles in promoting the weaning process; however, their impact on intestinal adaptation is unknown. The aim of this study was to investigate the impact of polyamines ingestion on adaptation and hepatic lipid metabolism in SBS. We performed resection of two-thirds of the small intestine in male Lewis rats as an SBS model. They were allocated into three groups and fed different polyamine content diets (0%, 0.01%, 0.1%) for 30 days. Polyamines were confirmed to distribute to remnant intestine, whole blood, and liver. Villous height and number of Ki-67-positive cells in the crypt area increased with the high polyamine diet. Polyamines increased secretory IgA and mucin content in feces, and enhanced tissue Claudin-3 expression. In contrast, polyamines augmented albumin synthesis, mitochondrial DNA copy number, and ATP storage in the liver. Moreover, polyamines promoted autophagy flux and activated AMP-activated protein kinase with suppression of lipogenic gene expression. Polyamines ingestion may provide a new therapeutic option for SBS with IFALD.
Topics: Rats; Animals; Male; Short Bowel Syndrome; Polyamines; Rats, Sprague-Dawley; Rats, Inbred Lew; Intestine, Small; Diet; Models, Theoretical; Intestinal Mucosa
PubMed: 38409241
DOI: 10.1038/s41598-024-55258-4 -
Antioxidants (Basel, Switzerland) Feb 2024International provenance trials are a hot topic in forestry, and in light of climate change, the search for more resilient beech provenances and their assisted migration...
International provenance trials are a hot topic in forestry, and in light of climate change, the search for more resilient beech provenances and their assisted migration is one of the challenges of climate-smart forestry. The main aim of the study was to determine intraspecific variability in European beech ( L.) among 11 beech provenances according to total antioxidant capacities estimated by various assays, such as DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid), FRAP (ferric reducing antioxidant power) assay, and radical scavenging capacity against nitric oxide (RSC-NO assays), as well as osmolyte content, primarily individual polyamines (putrescine, spermidine, and spermine), and free proline content. Polyamine amounts were quantified by using HPLC coupled with fluorescent detection after dansylation pretreatment. The highest values for radical scavenger capacity assays (ABTS, DPPH, and FRAP) were measured in the German provenances DE47 and DE49. Also, the highest NO inhibition capacity was found in the provenance DE49, while the highest content of proline (PRO), total phenolic content (TPC), and total flavonoid content (TFC) was recorded in DE47. The Austrian AT56 and German provenance DE49 were most abundant in total polyamines. This research underlines the importance of the application of common antioxidant assays as well as osmolyte quantification as a criterion for the selection of climate-ready beech provenances for sustainable forest management.
PubMed: 38397825
DOI: 10.3390/antiox13020227 -
Metabolomics : Official Journal of the... Feb 2024Thiazolidinediones (TZDs), represented by pioglitazone and rosiglitazone, are a class of cost-effective oral antidiabetic agents posing a marginal hypoglycaemia risk....
INTRODUCTION
Thiazolidinediones (TZDs), represented by pioglitazone and rosiglitazone, are a class of cost-effective oral antidiabetic agents posing a marginal hypoglycaemia risk. Nevertheless, observations of heart failure have hindered the clinical use of both therapies.
OBJECTIVE
Since the mechanism of TZD-induced heart failure remains largely uncharacterised, this study aimed to explore the as-yet-unidentified mechanisms underpinning TZD cardiotoxicity using a toxicometabolomics approach.
METHODS
The present investigation included an untargeted liquid chromatography-mass spectrometry-based toxicometabolomics pipeline, followed by multivariate statistics and pathway analyses to elucidate the mechanism(s)of TZD-induced cardiotoxicity using AC16 human cardiomyocytes as a model, and to identify the prognostic features associated with such effects.
RESULTS
Acute administration of either TZD agent resulted in a significant modulation in carnitine content, reflecting potential disruption of the mitochondrial carnitine shuttle. Furthermore, perturbations were noted in purine metabolism and amino acid fingerprints, strongly conveying aberrations in cardiac energetics associated with TZD usage. Analysis of our findings also highlighted alterations in polyamine (spermine and spermidine) and amino acid (L-tyrosine and valine) metabolism, known modulators of cardiac hypertrophy, suggesting a potential link to TZD cardiotoxicity that necessitates further research. In addition, this comprehensive study identified two groupings - (i) valine and creatine, and (ii) L-tryptophan and L-methionine - that were significantly enriched in the above-mentioned mechanisms, emerging as potential fingerprint biomarkers for pioglitazone and rosiglitazone cardiotoxicity, respectively.
CONCLUSION
These findings demonstrate the utility of toxicometabolomics in elaborating on mechanisms of drug toxicity and identifying potential biomarkers, thus encouraging its application in the toxicological sciences. (245 words).
Topics: Humans; Rosiglitazone; Pioglitazone; Myocytes, Cardiac; Cardiotoxicity; Diabetes Mellitus, Type 2; Metabolomics; Thiazolidinediones; Heart Failure; Amino Acids; Biomarkers; Carnitine; Valine
PubMed: 38393619
DOI: 10.1007/s11306-024-02097-z -
Heliyon Feb 2024This study was conducted to mitigate the food safety risks related to biogenic amine (BA) by reducing the BA content in using applicable food additives. In -...
This study was conducted to mitigate the food safety risks related to biogenic amine (BA) by reducing the BA content in using applicable food additives. In - experiments, of the additives tested, tartaric acid (TA), potassium sorbate (PS), and sodium benzoate (SB) considerably inhibited tyramine production of strains of spp. and while less affecting their growth. In addition to these three additives, two additives, glycine (GL) and nicotinic acid (NA), reported to have significant inhibitory effects in previous studies, were applied to the fermentation with prolific tyramine-producing strains of and . The content of tyramine in the samples treated with TA, PS, SB, GL, and NA was significantly reduced by 27.5%, 50.7%, 51.4%, 76.1%, and 100.0%, respectively, compared to the control sample. Additionally, the content of polyamines (putrescine, cadaverine, spermidine, and spermine) in the GL-treated sample was reduced by 42.6%-62.4%. The mode of action could be attributed to inhibiting the bacterial decarboxylase activity and/or growth. Consequently, excluding NA that interfered with fermentation, GL was the most outstanding additive with an inhibitory effect on tyramine formation in food, followed by SB and PS, all of which showed a more than 50% reduction. Therefore, the use of appropriate additives could be one of the promising strategies to avoid the food safety issues implicated in BAs in .
PubMed: 38379996
DOI: 10.1016/j.heliyon.2024.e26135