MARCH5 ameliorates aortic valve calcification via RACGAP1-DRP1 pathway associated mitochondrial quality control

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2025, Номер unknown, С. 119911 - 119911

Опубликована: Янв. 1, 2025

Язык: Английский

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ATM knock out alters calcium signalling and augments contraction in skeletal muscle cells differentiated from human urine-derived stem cells

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Апрель 15, 2025

Abstract Ataxia-telangiectasia (A-T) is a rare neurodegenerative disorder caused by the deficiency of serine/threonine kinase ataxia telangiectasia mutated (ATM) protein, whose loss function leads to altered cell cycle, apoptosis, oxidative stress balance and DNA repair after damage. The clinical manifestations are multisystemic, among them cerebellar degeneration muscular ataxia. molecular mechanism which ATM A-T still uncertain and, currently only symptomatic treatments available. In this study, we generated functional skeletal muscle model that recapitulates highlights role in calcium signalling contraction. To aim, using CRISPR/Cas9 technology, knocked out protein urine-derived stem cells (USCs) from healthy donors. resulting USCs-ATM-KO maintained stemness but showed G2/S cycle progression an inability UV Moreover, they increased cytosolic release ATP stimulation detriment mitochondria. alterations homoeostasis were differentiation into (USC-SkMCs) correlated with impaired Indeed, USC-SkMCs-ATM-KO contraction kinetics dramatically accelerated compared control cells. These results highlight relevant muscle, not dependent on non-functional neuronal communication, paving way for future studies interpretation

Язык: Английский

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Impaired arterial dilation and increased NOX2 generated oxidative stress in subjects with ataxia-telangiectasia mutated (ATM) kinase.

Redox Biology, Год журнала: 2024, Номер 77, С. 103347 - 103347

Опубликована: Сен. 13, 2024

Subjects with mutations in the Ataxia-Telangiectasia mutated (ATM) gene encoding for ATM kinase have a greater predisposition to develop atherosclerosis, but mechanism behind this phenomenon is not yet understood. NADPH oxidase type 2 may play role process, leading endothelial dysfunction and an increased susceptibility thrombosis. The purpose of study was assess redox state individuals determine its impact on function.

Язык: Английский

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USP15 regulates radiation-induced DNA damage and intestinal injury through K48-linked deubiquitination and stabilisation of ATM

Molecular Medicine, Год журнала: 2024, Номер 30(1)

Опубликована: Ноя. 9, 2024

Radiation-induced intestinal injury (RIII) interrupts the scheduled processes of abdominal and pelvic radiotherapy (RT) compromises quality life cancer survivors. However, specific regulators mechanisms underlying effects RIII remain unknown. The biological RT are caused primarily by DNA damage, ataxia telangiectasia mutated (ATM) is a core protein damage response (DDR). whether ATM regulated deubiquitination signaling remains unclear.

Язык: Английский

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Making PI3K superfamily enzymes run faster

Advances in Biological Regulation, Год журнала: 2024, Номер unknown, С. 101060 - 101060

Опубликована: Ноя. 1, 2024

Язык: Английский

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Novel pathogenic ATM mutation with ataxia-telangiectasia in a Chinese family

Frontiers in Genetics, Год журнала: 2024, Номер 15

Опубликована: Ноя. 28, 2024

Ataxia-Telangiectasia (A-T) is a rare, autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, and increased cancer risk. Mutations in the ATM gene, which essential for DNA damage repair, underlie this condition. This study reports novel homozygous frameshift mutation (ATM_ex20 c.3062delT, p. Val1021fs) Chinese family with two affected siblings. The mutation, located exon 20, has not been previously documented, expanding spectrum of mutations. proband her older sister presented classic A-T symptoms, including gait instability conjunctival telangiectasia. Both siblings low immunoglobulin A (IgA) levels, slightly elevated IgM alpha-fetoprotein (AFP). Cranial magnetic resonance imaging (MRI) findings revealed atrophy cerebral white matter lesions both sisters. Interestingly, while sisters shared same their clinical severity differed, highlighting complexity genotype-phenotype correlations A-T. parents an unaffected were heterozygous carriers, consistent inheritance. underscores importance genetic testing diagnosis provides new insights into diversity ATM-related diseases. Further research needed to understand broader implications mutation.

Язык: Английский

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PFKFB3-dependent redox homeostasis and DNA repair support cell survival under EGFR-TKIs in non-small cell lung carcinoma

Cancer & Metabolism, Год журнала: 2024, Номер 12(1)

Опубликована: Дек. 18, 2024

Язык: Английский

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