bims-glecem 2023-06-25 papers

Issue of 2023–06–25
six papers selected by
Dipsikha Biswas, Københavns Universitet

Front Physiol. 2023 ;14 1229040

Editorial: Strategies to fight exercise intolerance in neuromuscular disorders, volume II.

Francesca Lanfranconi, Lucio Tremolizzo, Mauro Marzorati, Giuseppe D'Antona.

Keywords: diet; disability; exercise; glycogen storage diseases; inclusion; motor neuron disease; neuromuscular degenerative diseases

DOI: https://doi.org/10.3389/fphys.2023.1229040

Tissue Cell. 2023 Jun 12. pii: S0040-8166(23)00128-3. [Epub ahead of print]83 102140

Glycogen in retinal horizontal cells of the African mud catfish Clarias gariepinus (Burchell, 1822) and its physiological significance.

Tapas C Nag, Bhaskar Sharma, Shilpa Gorla.

This paper reports on glycogen store in the retinal horizontal cells (HC) of the African mud catfish Clarias gariepinus, as seen by histochemical reaction with periodic acid Schiff (PAS) and transmission electron microscopy in light- as well as dark-adapted state. Glycogen is abundant in the large somata and less in their axons, characterised ultrastructurally by many microtubules and extensive gap junctions interconnecting them. There was no apparent difference in glycogen content in HC somata between light- and dark adaptation, but the axons clearly showed absence of glycogen in dark condition. The HC somata (presynaptic) make synapses with dendrites in the outer plexiform layer. Müller cell inner processes, which contain more densely packed glycogen, invest the HC. Other cells of the inner nuclear layer do not show any appreciable content of glycogen. Rods, but not cones, contain abundant glycogen in their inner segments and synaptic terminals. It is likely that glycogen is used as energy substrate in hypoxia for this species that dwell muddy aquatic environment with low oxygen content. They appear to have high energy demand, and a high glycogen content in HC could act as a ready source to fulfil physiological processes, like microtubule-based transport of cargo from the large somata to axons and the maintenance of electrical activities across the gap junctions between the axonal processes. It is also likely that they can supplement glucose to the neighbouring inner nuclear layer neurons, which are clearly devoid of glycogen.

Keywords: Catfish; Glycogen; Horizontal cells; Periodic acid Schiff reaction; Photoreceptor cells; Retina

DOI: https://doi.org/10.1016/j.tice.2023.102140

Vasc Specialist Int. 2023 Jun 19. 39 14

Von Gierke Disease (Glycogen Storage Disease Type I) and Life-Threatening Abdominal Aortic Aneurysm: A Case Report of an Extremely Rare Condition.

Apostolos G Pitoulias, Nizar Abu Bakr, Majid Kazemtash, Firouza Dahi, Michael Schütz, Konstantinos P Donas.

Von Gierke disease, also known as glycogen storage disease type I, co-existent with an abdominal aortic aneurysm (AAA), is an extremely rare combination of diseases that requires challenging therapeutic measures. We present, for the first time in literature, the case of a 62-year-old female with von Gierke disease who required open surgical repair of an AAA with challenging neck anatomy outside of instructions for use of endovascular repair. Even though the surgical risks for life-threatening complications, such as pancreatitis, metabolic acidosis, and kidney failure, were high, the 6-month postoperative course was uneventful. Despite the invasiveness of the treatment, surgery to treat the AAA was safe and effective. Further data is needed to draw robust conclusions about the treatment of choice for those patients with diseases in co-existence with AAAs.

Keywords: Abdominal aortic aneurysm; Glycogen storage disease; Open repair; von Gierke disease

DOI: https://doi.org/10.5758/vsi.230017

Bioorg Chem. 2023 Jun 13. pii: S0045-2068(23)00324-3. [Epub ahead of print]138 106663

Synthesis and biological evaluation of thieno[3,2-c]pyrazol-3-amine derivatives as potent glycogen synthase kinase 3β inhibitors for Alzheimer's disease.

Ning Yan, Fei Xie, Long-Qian Tang, De-Feng Wang, Xiang Li, Chao Liu, Zhao-Peng Liu.

Glycogen synthase kinase 3β (GSK-3β) is a potential target for anti-Alzheimer's disease (AD) drug development. In this study, a series of novel thieno[3,2-c]pyrazol-3-amine derivatives was synthesized and evaluated as potential GSK-3β inhibitors by structure-based drug design. The thieno[3,2-c]pyrazol-3-amine derivative 54 with a 4-methylpyrazole moiety which interacted with Arg141 by π-cation interaction was identified as a potent GSK-3β inhibitor with an IC50 of 3.4 nM and an acceptable kinase selectivity profile. In the rat primary cortical neurons, compound 54 showed neuroprotective effects on Aβ-induced neurotoxicity. Western blot analysis indicated that 54 inhibited GSK-3β by up-regulating the expression of phosphorylated GSK-3β at Ser9 and down-regulating the expression of phosphorylated GSK-3β at Tyr216. Meanwhile, 54 decreased tau phosphorylation at Ser396 in a dose-dependent way. In astrocytes and microglia cells, 54 inhibited the expression of inducible nitric oxide synthase (iNOS), indicating that 54 showed an anti-neuroinflammatory effect. In the AlCl3-induced zebrafish AD model, 54 significantly ameliorated the AlCl3-induced dyskinesia, demonstrating its anti-AD activity in vivo.

Keywords: Alzheimer’s disease; Aβ; GSK-3β inhibitors; Neuroinflammation; Tau hyperphosphorylation

DOI: https://doi.org/10.1016/j.bioorg.2023.106663

Med Oncol. 2023 Jun 22. 40(7): 211

Identification of glycogen phosphorylase L as a potential target for lung cancer.

Xin-Ling He, Wen-Yu Lyu, Xin-Yuan Li, Hong Zhao, Lu Qi, Jin-Jian Lu.

Traditional Chinese medicine (TCM) has been widely used for cancer treatment. Identification of anti-cancer targets of TCM is the first and principal step in discovering molecular mechanisms of TCM as well as obtaining novel targets for cancer therapy. In this study, glycogen phosphorylase L (PYGL) was identified as one of the targeted proteins for several TCMs and was upregulated in various cancer types. The expression level of PYGL was positively correlated with the stage of lung cancer and the poor prognosis of patients. Meanwhile, knockdown of PYGL significantly inhibited proliferation and migration in lung cancer cells. In addition, PYGL was associated with spindle, kinetochore, and microtubule, the cellular components that are closely related to mitosis, in lung cancer. Moreover, PYGL was more susceptible to be upregulated by 144 mutated genes. Taken together, PYGL is a potential target for lung cancer treatment and its molecular mechanism probably influences the mitotic function of cells by regulating energy metabolism.

Keywords: Glycogen phosphorylase; Lung cancer; Mitosis; PYGL; Target; Traditional Chinese medicine

DOI: https://doi.org/10.1007/s12032-023-02069-8

Lipids Health Dis. 2023 Jun 21. 22(1): 78

Combining albumin deficiency and acute exercise reduces hepatic lipid droplet size in mice.

Yi Zhang, Mirandia Szramowski, Shuhan Sun, Gregory C Henderson.

Hepatic lipid droplets (LDs) are implicated in ectopic lipid accumulation. The core of LDs, triacylglycerol (TAG), is synthesized from the esterification of fatty acids to a glycerol-3-phosphate (G-3-P) backbone. Albumin transports plasma free fatty acids, and previously albumin knockout (Alb-/-) mice were shown to exhibit lower hepatic TAG levels than wildtype (WT). Exercise is a beneficial strategy to alter hepatic metabolism, but its impacts on reducing hepatic lipids are far from satisfactory. The aim of this study was to investigate the combined effect of albumin deficiency and acute exercise on hepatic LDs. Eight-week-old male Alb-/- and WT mice were divided into sedentary and exercise groups. Exercised mice performed a 30-min high-intensity exercise bout. Results showed that sedentary Alb-/- mice had smaller hepatic LDs (P < 0.0001), associated with mitochondria, while WT mice exhibited larger LDs, surrounded by glycogen granules. Following acute exercise, hepatic LDs in Alb-/- mice reduced by 40% in size, while in WT increased by 14% (P < 0.0001). The maintenance of WT hepatic LDs was associated with elevated G-3-P level (P < 0.05), potentially derived from glycogen (R = -0.32, %change in glycogen versus LD content, P < 0.05). The reduction in Alb-/- mice LDs after exercise was possibly due to their low glycogen level. In conclusion, Alb-/- mice exhibited an enhanced capacity for reducing hepatic LD size and content in response to exercise. These findings suggest that modulating albumin's functions combined with exercise could be a potential strategy to reduce ectopic lipid deposition in the liver.

DOI: https://doi.org/10.1186/s12944-023-01845-9