Ask about this productRelated genes to: AKAP5 Blocking Peptide
- Gene:
- AKAP5 NIH gene
- Name:
- A-kinase anchoring protein 5
- Previous symbol:
- -
- Synonyms:
- AKAP75, AKAP79
- Chromosome:
- 14q23.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-09-16
- Date modifiied:
- 2015-11-17
Related products to: AKAP5 Blocking Peptide
Related articles to: AKAP5 Blocking Peptide
- Regular physical activity is an effective non-pharmacological approach to hypertension management and maternal exercise improves offspring cardiovascular health, although mechanisms remain unclear. A-kinase anchoring protein 150 (AKAP150) targets protein kinase Cα to L-type Ca channels (Ca1.2), enhancing vascular tone in arterial smooth muscle during hypertension. This study aims to uncover a novel mechanism in which epigenetic modifications of the AKAP150 gene (Akap5) mediate the beneficial effects of maternal exercise on vascular function in hypertensive offspring. - Source: PubMed
Publication date: 2026/02/04
Qiu FangZhang YanyanShan MeilingCao JiaqiFan ZihanXu ZhaoxiaDing XiaozhenLiu XiaodongShi Lijun - Neuropathic pain is characterized by hyperalgesia, allodynia or spontaneous pain arising from lesions or pathology in the somatosensory nervous system. Multiple mechanisms contribute to this pain following peripheral nerve and spinal cord injuries. Evidence shows that injury-induced changes in dendritic spine morphology in the dorsal horn may contribute to neuropathic pain presentation. Dendritic spines, critical postsynaptic structures for synaptic transmission, undergo remodelling from filopodia-like structures to mature, mushroom-shaped spines in nociceptive spinal cord regions after injury. Recent evidence indicates that peripheral nerve and spinal cord injuries affect local tissues and also lead to pathology in supraspinal brain regions. Interestingly, different injuries appear to target specific brain regions, potentially causing corresponding remodelling of dendritic spines. To investigate this, we examined whether spared nerve injury, as a peripheral nerve injury model, and spinal cord injury induce morphological changes in dendritic spines in different brain regions and whether systemic administration of mesenchymal stem cells could alleviate neuropathic pain by altering dendritic spine morphology. Our results demonstrate that both injuries induce significant morphological changes in dendritic spines in the brain and spinal cord. Specifically, the peripheral nerve injury model increases the density of mushroom-shaped spines in superficial Lamina II of the dorsal horn, whereas spinal cord injury induces similar changes in deeper Lamina V. In the brain, the peripheral nerve injury model showed increased mushroom-shaped spines in the sensory cortex and ventral posterior complex of the thalamus. In contrast, the spinal cord injury model showed these changes primarily in the thalamic intralaminar nuclei. Infused mesenchymal stem cells partially alleviated neuropathic pain in both models and reduced the density of mushroom-shaped spines in the respective affected regions. Gene expression analysis of cytoskeletal genes related to actin associated with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AKAP5, ACTR2, and SORBS2) revealed upregulation of these genes in the sensory cortex (in the peripheral nerve injury model) and the thalamus (in the spinal cord injury model). Mesenchymal stem cells suppressed these upregulations, which were associated with reduced neuropathic pain. These findings suggest that infused mesenchymal stem cells can protect against the abnormal remodelling of dendritic spines, thereby contributing to pain alleviation regardless of injury type or affected region. The systemic administration of mesenchymal stem cells thus offers a promising therapeutic approach for treating multiple neuropathic pain conditions through structural and molecular alterations in dendritic spines. - Source: PubMed
Publication date: 2025/12/15
Fukushi RyunosukeSasaki MasanoriObara HisashiKurihara KotaHirota RyosukeMorita TomonoriTeramoto AtsushiYamashita ToshihikoTan Andrew MWaxman Stephen GKocsis Jeffery DHonmou Osamu - TREK-1 (K2.1) and TREK-2 (K10.1) background K channels are widely expressed determinants of cellular excitability. We examined the regulation of TREK channels by the increase of cytoplasmic calcium concentration in Xenopus oocytes. Extracellular application of ionomycin, as well as the microinjection of inositol 1,4,5-trisphosphate (IP), evoked TREK-1 activation, whereas the microinjection of EGTA prevented the effect. TRAAK (K4.1) was not affected, whereas TREK-2 was activated by ionomycin in the presence of ML-335 K activator compound. Cyclosporin A and FK506, specific inhibitors of the calcium/calmodulin-dependent protein phosphatase (calcineurin), abrogated the activation of TREK channels by ionomycin. Coexpression of a constitutively active form of calcineurin with TREK-1 increased the background K current, but FK506 restored the basal channel activity. Mutations of TREK-1 phosphorylation sites (S300A/S333A) eliminated the response to ionomycin. Coexpression of the known interaction partner AKAP5 (AKAP79/AKAP150) with TREK-1 significantly enhanced the calcium-dependent activation. The wild-type anchoring protein induced higher TREK activation than a dominant negative AKAP5 construct carrying mutations in the PXIXIT-like calcineurin binding site. In conclusion, TREK-1 and TREK-2 are regulated in a calcium-dependent manner, in addition to the previously described TRESK (K18.1), however, TREK channels are activated by calcineurin anchored to AKAP5. - Source: PubMed
Publication date: 2025/12/29
Baukál DóraPergel EnikőDebreczeni DorinaHorváth ÁrminTóth Dániel JTakács Panna TCzirják Gábor - Epilepsy is a chronic and refractory neurological disorder, with drug resistance remaining a major challenge. Identifying new therapeutic targets could facilitate the development of more effective anti-seizure medications. AKAP79/150, a member of A-Kinase Anchoring Proteins (AKAPs) family, plays a critical role in synaptic transmission and plasticity. Although its implication in early epileptogenesis has been reported, its role in epilepsy progression remains unclear. In this study, using a kainic acid (KA)-induced epilepsy mouse model, we found that the expression and palmitoylation of AKAP150 in the hippocampus were significantly upregulated during epilepsy development. Silencing AKAP150 by the right intracerebroventricular (ICV) siRNA injections or inhibiting its palmitoylation by 2-bromohexadecanoic acid attenuated KA-induced epilepsy, as evidenced by reduced seizure severity, duration, and frequency of spontaneous recurrent seizures within 14 days. Mechanistically, AKAP79/150 interacts with protein kinase C (PKC) to suppress KCNQ expression, thereby diminishing inhibitory M-currents and contributing to epileptogenesis. Our findings reveal the pivotal role of AKAP79/150 in epilepsy progression and highlight its potential as a therapeutic target for epilepsy intervention. - Source: PubMed
Publication date: 2025/11/02
Chu Chen-ChaoHu Ya-HuiZhang Hai-FengLi Gui-ZhouWu Shi-YuZang Yan-YuChen JiangWang Hao-YuXu Yang-YangGuo Hong-LiShi Yun StoneChen Feng - Over the past few decades, a significant change globally in sugar intake has coincided with a rising incidence of male infertility, which is now a major public health concern. Diets rich in fructose have been implicated in both male infertility and increased susceptibility to metabolic disorders, such as obesity, diabetes, and related heart problems. While fructose is known to be present in seminal fluid and crucial for sperm motility, the precise role of fructose in testicular function remains largely unknown. GLUT5 is an exclusive fructose transporter essential for dietary fructose uptake in the intestine. It is also expressed mainly in germ and Leydig cells. We recently revealed that disrupting the Glut5 gene in male mice impairs spermatogenesis and steroidogenesis. However, its specific role within Leydig cells remains unexplored. Therefore, we investigated its role by inhibiting GLUT5 in a murine Leydig cell line (mLTC-1) using a specific inhibitor of GLUT5, MSNBA, combined with a multi-omics approach. Exposing mLTC-1 cells to MSNBA reduced the intracellular fructose content, limited cell proliferation, and enhanced progesterone and androgens production (Δ4-androstenedione and testosterone). The latter was associated with the upregulation of two genes and proteins involved in steroidogenesis, such as Hsd3b and steroidogenic acute regulatory protein (StAR). GLUT5 inhibition in mLTC-1 cells also modified lipid and carbohydrate metabolism. Lipidomic analysis showed decreased cholesterol esters and a shift in the ratio of polyunsaturated fatty acids (PUFAs) to monounsaturated fatty acids (MUFAs). These lipid changes correlated with alterations in the expression of mRNA-encoding enzymes involved in lipogenesis, such as ELOVL6. Metabolomics analysis showed a reduction in most glycolysis metabolites, except for pyruvate and lactate. However, pyruvate could conserve its level by a production through an amino acid pathway using the higher branched-chain amino acid content. Nevertheless, the activity of mitochondria measured by seahorse was not altered. The transcriptomic analysis performed by BRB-seq approach revealed an upregulation of several androgen-sensitive genes, such as Akap5, Slc39a9, an androgen receptor or lactate dehydrogenase A (Ldha), which produces lactate, and downregulation of several genes associated with the insulin pathway such as Tsc2 or the hexokinase Hkdc1. In conclusion, GLUT5 supported fructose intake in the murine Leydig cell line mLTC-1, leading to a reduction in cell proliferation. The consequences of inhibition of GLUT5 led to an increase in fatty acids cell content, a perturbation in glycolysis and amino-acid metabolism but an enhanced androgen production. Since androgens regulate spermatogenesis, hyperandrogenism induced by a lower fructose content in Leydig cells may be a primary cause leading to the disruption of sperm production and quality, as well as sexual behavior, as described in the GLUT5 KO mouse model. - Source: PubMed
Publication date: 2025/09/12
Kallianioti AikateriniBourdon GuillaumeChevaleyre ClairePéchoux ChristineRamé ChristelleBourgeais JérômeHérault OlivierGeoffre NancyDarde ThomasPlotton IngridDouard VéroniqueDupont JoëlleFroment Pascal