BNIP3 Is Involved in Muscle Fiber Atrophy in Late-Onset Pompe Disease Patients

Carrasco‐Rozas, Ana; Fernández‐Simón, Esther; Suárez‐Calvet, Xavier; Piñol-Jurado, Patricia; Alonso‐Pérez, Jorge; Luna, Noemí de; Schöser, Benedikt; Meinke, Peter; Domínguez‐González, Cristina; Hernández-Laín, Aurelio; Paradas, Carmen; Rivas, Eloy; Illa, Isabel; Olivé, Montse; Gallardo, Eduard; Díaz‐Manera, Jordi

doi:10.1016/j.ajpath.2022.05.003

Cited by 4 publications

(5 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we confirmed significant associations between the genotypes of SNP (chr2:36812553) in BMF and two SNPs (chr12:31782870, chr12:31781825) in NAD-ME with the shear force (SF) for geese meat. BMF , a member of the Bcl2 protein family, is a sensor for intracellular damage that can trigger cell apoptosis and potentially mediate muscle fiber atrophy [ 47 , 48 ]. NAD-ME participates in various metabolic pathways and provides reducing power NADPH for the synthesis of various cellular components [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of SNPs Associated with Goose Meat Quality Traits Using a Genome-Wide Association Study Approach

Gao,

Zhang,

Huang

et al. 2023

Animals

View full text Add to dashboard Cite

(1) Background: Goose meat is highly valued for its economic significance and vast market potential due to its desirable qualities, including a rich nutritional profile, tender texture, relatively low-fat content, and high levels of beneficial unsaturated fatty acids. However, there is an urgent need to improve goose breeding by identifying molecular markers associated with meat quality. (2) Methods: We evaluated meat quality traits, such as meat color, shear force (SF), cooking loss rate (CLR), and crude fat content (CFC), in a population of 215 male Sichuan white geese at 70 days of age. A GWAS was performed to identify potential molecular markers associated with goose meat quality. Furthermore, the selected SNPs linked to meat quality traits were genotyped using the MALDI-TOP MS method. (3) Results: A dataset of 2601.19 Gb of WGS data was obtained from 215 individuals, with an average sequencing depth of 10.89×. The GWAS revealed the identification of 43 potentially significant SNP markers associated with meat quality traits in the Sichuan white goose population. Additionally, 28 genes were identified as important candidate genes for meat quality. The gene enrichment analysis indicated a substantial enrichment of genes within a 1Mb vicinity of SNPs in both the protein digestion and absorption pathway and the Glycerolipid metabolism pathway. (4) Conclusion: This study provides valuable insights into the genetic and molecular mechanisms underlying goose meat quality traits, offering crucial references for molecular breeding in this field.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of SNPs Associated with Goose Meat Quality Traits Using a Genome-Wide Association Study Approach

Gao,

Zhang,

Huang

et al. 2023

Animals

View full text Add to dashboard Cite

show abstract

“…For cell culture studies, primary myoblasts were isolated, cultured and differentiated as previously described (33). To measure cytoplasmic Ca 2+ , cell cultures were incubated with 2 µM Fluo-4 (Invitrogen) for 20 minutes at RT, followed by wash (twice) with a physiological buffer containing 132 mM NaCl, 0,33 mM NaH2PO4, 4 mM KCl, 4 mM NaHCO3, 2 mM CaCl2, 1,6 mM MgCl2, 10 mM HEPES, 5 mM glucose and 5 mM pyruvic acid.…”

Section: Functional Studies To Assess Ca 2+ Kinetics After Sarcolemma...mentioning

confidence: 99%

A homozygousATP2A2variant alters sarcoendoplasmic reticulum Ca²⁺-ATPase 2 function in skeletal muscle and causes a novel vacuolar myopathy

Llansó,

Ravenscroft,

Aceituno

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Sarcoendoplasmic reticulum Ca2+-ATPase isoform 2 (SERCA2), encoded by ATP2A2, is a key protein involved in intracellular Ca2+ homeostasis. The transcript SERCA2a is predominantly expressed in cardiac muscle and in type I myofibers, while SERCA2b is ubiquitously expressed including in skin cells. To date, variants in this gene were reported to be the cause of Darier disease, an autosomal dominant dermatologic disorder, but have never been linked to primary skeletal muscle disease. We describe four patients suffering from a novel hereditary myopathy caused by a homozygous missense variant in ATP2A2. Methods: We studied a family with four affected individuals suffering from an adult-onset progressive skeletal myopathy. We performed a comprehensive evaluation of the clinical phenotype, serum CK levels, muscle MRI, and muscle biopsy, with genetic workup by means of gene panel sequencing followed by whole genome sequencing and segregation analysis. Immunohistochemistry and western blot (WB) to evaluate SERCA2 and SERCA1 expression in skeletal muscle was performed. We evaluated kinetics of Ca2+ handling following caffeine exposure or voltage-induced sarcolemma depolarization in patient myoblasts and myotubes, compared to healthy controls. Results: Four siblings in their fifties developed in early adulthood symmetric proximal weakness in lower limbs, which was slowly progressive over time. They had no skin or cardiac involvement. Biopsy findings in two affected individuals showed small vacuoles restricted to type I myofibers. Ultrastructural analysis showed dilation and proliferation of T-tubules, swelling of sarcoplasmic reticulum and autophagic vacuoles. Genome sequencing revealed a homozygous variant in ATP2A2 (c.1117G>A, p.(Glu373Lys)) which segregated with the disease. Immunohistochemistry suggested SERCA2 mislocalization in patient myofibers compared to controls. WB did not show changes in the amount or molecular weight of the protein. In vitro functional studies revealed delayed sarcoendoplasmic reticulum Ca2+ reuptake in patient myotubes, consistent with an altered pumping capacity of SERCA2 after cell stimulation with caffeine or depolarization. Conclusions: We report a novel adult-onset vacuolar myopathy caused by a homozygous variant in ATP2A2, resulting in a pure skeletal muscle phenotype with a limb-girdle distribution. Biopsy findings and functional studies demonstrating an impaired function of SERCA2 and consequent Ca2+ dysregulation in slow-twitch skeletal myofibers highly support the pathogenicity of the variant.

show abstract

“…This finding is mainly observed because the total number of muscle fibers does not show an apparent change, and the main factor determining the muscle fiber area is the protein synthesis rate of muscle fibers [129]. In FGF21-knockout mice, the rate of protein synthesis is higher than that of oxidation, and the expression of BCL2-interacting protein 3 (Bnip3) is inhibited [130]. Bnip3 is a pro-apoptotic protein, and the inhibition of Bnip3 expression downregulates autophagy, thereby protecting against muscle atrophy and total muscle loss [130].…”

Section: Fgf21 Regulates Multiple Pathways To Mediate Myogenic Differ...mentioning

confidence: 99%

“…In FGF21-knockout mice, the rate of protein synthesis is higher than that of oxidation, and the expression of BCL2-interacting protein 3 (Bnip3) is inhibited [130]. Bnip3 is a pro-apoptotic protein, and the inhibition of Bnip3 expression downregulates autophagy, thereby protecting against muscle atrophy and total muscle loss [130]. However, under the condition of FGF21 overexpression, the protein synthesis rate is less than the protein oxidation rate, which stimulates the expression of Bnip3 protein and acts on FGF21, resulting in a reduction in the muscle fiber area and muscle atrophy [129].…”

Section: Fgf21 Regulates Multiple Pathways To Mediate Myogenic Differ...mentioning

confidence: 99%

Fibroblast Growth Factor 21: A Fascinating Perspective on the Regulation of Muscle Metabolism

Li,

Chen,

Wei

et al. 2023

IJMS

View full text Add to dashboard Cite

Fibroblast growth factor 21 (FGF21) plays a vital role in normal eukaryotic organism development and homeostatic metabolism under the influence of internal and external factors such as endogenous hormone changes and exogenous stimuli. Over the last few decades, comprehensive studies have revealed the key role of FGF21 in regulating many fundamental metabolic pathways, including the muscle stress response, insulin signaling transmission, and muscle development. By coordinating these metabolic pathways, FGF21 is thought to contribute to acclimating to a stressful environment and the subsequent recovery of cell and tissue homeostasis. With the emphasis on FGF21, we extensively reviewed the research findings on the production and regulation of FGF21 and its role in muscle metabolism. We also emphasize how the FGF21 metabolic networks mediate mitochondrial dysfunction, glycogen consumption, and myogenic development and investigate prospective directions for the functional exploitation of FGF21 and its downstream effectors, such as the mammalian target of rapamycin (mTOR).

show abstract

BNIP3 Is Involved in Muscle Fiber Atrophy in Late-Onset Pompe Disease Patients

Cited by 4 publications

References 58 publications

Identification of SNPs Associated with Goose Meat Quality Traits Using a Genome-Wide Association Study Approach

Identification of SNPs Associated with Goose Meat Quality Traits Using a Genome-Wide Association Study Approach

A homozygousATP2A2variant alters sarcoendoplasmic reticulum Ca²⁺-ATPase 2 function in skeletal muscle and causes a novel vacuolar myopathy

Fibroblast Growth Factor 21: A Fascinating Perspective on the Regulation of Muscle Metabolism

Contact Info

Product

Resources

About

BNIP3 Is Involved in Muscle Fiber Atrophy in Late-Onset Pompe Disease Patients

Cited by 4 publications

References 58 publications

Identification of SNPs Associated with Goose Meat Quality Traits Using a Genome-Wide Association Study Approach

Identification of SNPs Associated with Goose Meat Quality Traits Using a Genome-Wide Association Study Approach

A homozygousATP2A2variant alters sarcoendoplasmic reticulum Ca2+-ATPase 2 function in skeletal muscle and causes a novel vacuolar myopathy

Fibroblast Growth Factor 21: A Fascinating Perspective on the Regulation of Muscle Metabolism

Contact Info

Product

Resources

About

A homozygousATP2A2variant alters sarcoendoplasmic reticulum Ca²⁺-ATPase 2 function in skeletal muscle and causes a novel vacuolar myopathy