bims-glecem 2024-02-25 papers

Issue of 2024–02–25
four papers selected by
Dipsikha Biswas, Københavns Universitet

Scand J Med Sci Sports. 2024 Feb;34(2): e14571

Assessments of individual fiber glycogen and mitochondrial volume percentages reveal a graded reduction in muscle oxidative power during prolonged exhaustive exercise.

Joachim Nielsen, Rasmus Jensen, Niels Ørtenblad.

During submaximal exercise, there is a heterogeneous recruitment of skeletal muscle fibers, with an ensuing heterogeneous depletion of muscle glycogen both within and between fiber types. Here, we show that the mean (95% CI) mitochondrial volume as a percentage of fiber volume of non-glycogen-depleted fibers was 2 (-10:6), 5 (-21:11), and 12 (-21:-2)% lower than all the sampled fibers after continuing exercise for 1, 2 h, and until task failure, respectively. Therefore, a glycogen-dependent fatigue of individual fibers during submaximal exercise may reduce the muscular oxidative power. These findings suggest a relationship between glycogen and mitochondrial content in individual muscle fibers, which is important for understanding fatigue during prolonged exercise.

Keywords: exercise; fatigue; glycogen; mitochondria; muscle fiber; transmission electron microscopy

DOI: https://doi.org/10.1111/sms.14571

Pediatr Discov. 2023 ;pii: e3. [Epub ahead of print]1(2):

Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies.

Jiamin Zhong, Yannian Gou, Piao Zhao, Xiangyu Dong, Meichun Guo, Aohua Li, Ailing Hao, Hue H Luu, Tong-Chuan He, Russell R Reid, Jiaming Fan.

Glycogen storage disease type I (GSDI) is an inherited metabolic disorder characterized by a deficiency of enzymes or proteins involved in glycogenolysis and gluconeogenesis, resulting in excessive intracellular glycogen accumulation. While GSDI is classified into four different subtypes based on molecular genetic variants, GSDIa accounts for approximately 80%. GSDIa and GSDIb are autosomal recessive disorders caused by deficiencies in glucose-6-phosphatase (G6Pase-α) and glucose-6-phosphate-transporter (G6PT), respectively. For the past 50 years, the care of patients with GSDI has been improved following elaborate dietary managements. GSDI patients currently receive dietary therapies that enable patients to improve hypoglycemia and alleviate early symptomatic signs of the disease. However, dietary therapies have many limitations with a risk of calcium, vitamin D, and iron deficiency and cannot prevent long-term complications, such as progressive liver and renal failure. With the deepening understanding of the pathogenesis of GSDI and the development of gene therapy technology, there is great progress in the treatment of GSDI. Here, we review the underlying molecular genetics and the current clinical management strategies of GSDI patients with an emphasis on promising experimental gene therapies.

Keywords: dietary therapy; drug therapy; gene therapy; glycogen storage disease type I; molecular genetics mechanism

DOI: https://doi.org/10.1002/pdi3.3

Mol Neurobiol. 2024 Feb 17.

Therapeutic Potential Effect of Glycogen Synthase Kinase 3 Beta (GSK-3β) Inhibitors in Parkinson Disease: Exploring an Overlooked Avenue.

Areej Turkistani, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Ali K Albuhadily, Athanasios Alexiou, Marios Papadakis, Mohamed M Elfiky, Hebatallah M Saad, Gaber El-Saber Batiha.

Parkinson's disease (PD) is a progressive neurodegenerative disease of the brain due to degeneration of dopaminergic neurons in the substantia nigra (SN). Glycogen synthase kinase 3 beta (GSK-3β) is implicated in the pathogenesis of PD. Therefore, the purpose of the present review was to revise the mechanistic role of GSK-3β in PD neuropathology, and how GSK-3β inhibitors affect PD neuropathology. GSK-3 is a conserved threonine/serine kinase protein that is intricate in the regulation of cellular anabolic and catabolic pathways by modulating glycogen synthase. Over-expression of GSK-3β is also interconnected with the development of different neurodegenerative diseases. However, the underlying mechanism of GSK-3β in PD neuropathology is not fully clarified. Over-expression of GSK-3β induces the development of PD by triggering mitochondrial dysfunction and oxidative stress in the dopaminergic neurons of the SN. NF-κB and NLRP3 inflammasome are activated in response to dysregulated GSK-3β in PD leading to progressive neuronal injury. Higher expression of GSK-3β in the early stages of PD neuropathology might contribute to the reduction of neuroprotective brain-derived neurotrophic factor (BDNF). Thus, GSK-3β inhibitors may be effective in PD by reducing inflammatory and oxidative stress disorders which are associated with degeneration of dopaminergic in the SN.

Keywords: GSK-3β; Parkinson’s disease

DOI: https://doi.org/10.1007/s12035-024-04003-z

Biology (Basel). 2024 Feb 18. pii: 127. [Epub ahead of print]13(2):

Exogenous Trehalose Improves Growth, Glycogen and Poly-3-Hydroxybutyrate (PHB) Contents in Photoautotrophically Grown Arthrospira platensis under Nitrogen Deprivation.

Nat-Anong Mudtham, Authen Promariya, Chanchanok Duangsri, Cherdsak Maneeruttanarungroj, Suchanit Ngamkala, Nattaphong Akrimajirachoote, Sorawit Powtongsook, Tiina A Salminen, Wuttinun Raksajit.

Glycogen and poly-3-hydroxybutyrate (PHB) are excellent biopolymer products from cyanobacteria. In this study, we demonstrate that nitrogen metabolism is positively influenced by the exogenous application of trehalose (Tre) in Arthrospira platensis under nitrogen-deprived (-N) conditions. Cells were cultivated photoautotrophically for 5 days under -N conditions, with or without the addition of exogenous Tre. The results revealed that biomass and chlorophyll-a content of A. platensis experienced enhancement with the addition of 0.003 M and 0.03 M Tre in the -N medium after one day, indicating relief from growth inhibition caused by nitrogen deprivation. The highest glycogen content (54.09 ± 1.6% (w/w) DW) was observed in cells grown for 2 days under the -N + 0.003 M Tre condition (p < 0.05), while the highest PHB content (15.2 ± 0.2% (w/w) DW) was observed in cells grown for 3 days under the -N + 0.03 M Tre condition (p < 0.05). The RT-PCR analysis showed a significant increase in glgA and phaC transcript levels, representing approximately 1.2- and 1.3-fold increases, respectively, in A. platensis grown under -N + 0.003 M Tre and -N + 0.03 M Tre conditions. This was accompanied by the induction of enzyme activities, including glycogen synthase and PHA synthase with maximal values of 89.15 and 0.68 µmol min-1 mg-1 protein, respectively. The chemical structure identification of glycogen and PHB from A. platensis was confirmed by FTIR and NMR analysis. This research represents the first study examining the performance of trehalose in promoting glycogen and PHB production in cyanobacteria under nitrogen-deprived conditions.

Keywords: Arthrospira platensis; PHA synthase; PHB; glgA; phaC; trehalose

DOI: https://doi.org/10.3390/biology13020127