Expression profile of the proapoptotic protein Bax in the human brain

Yao, Qi; Zhang, Huaiyuan; Standish, Collin; Grube, Joshua; Mañas, Adriana; Xiang, Jialing

doi:10.1007/s00418-022-02146-5

Cited by 3 publications

(2 citation statements)

References 56 publications

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“…There the authors demonstrated that nuclear BAX increased proliferation in lung carcinoma epithelial cells. Cytosolic and nuclear location of BAX has also been observed in lung cancer cells [25, 26] and in human brain cells [27]. Thereby, it seems that the specific cellular location of BAX is important for its role and that cytosolic location represents an inactive form of BAX, mitochondrial BAX is involved in apoptosis, and that nuclear BAX can increase cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Fractionated irradiation of murine salivary glands resulted in focal acinar cell atrophy, immune cell infiltration, fibrosis, and hyposalivation

Juvkam,

Zlygosteva,

Malinen

et al. 2023

Preprint

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Background: Radiotherapy of head and neck cancer may cause detrimental late side effects such as fibrosis and hyposalivation. Our aim was to investigate late radiation-induced cellular and molecular changes of the salivary glands after fractionated irradiation to the head and neck in a murine model. Methods: 12-week-old female C57BL/6J mice were irradiated with X-rays to a total dose of 66 Gy, given in 10 fractions over 5 days. The radiation field covered the oral cavity and major salivary glands. Salivary gland function was assessed by collecting saliva at baseline and at various time points after irradiation. The submandibular (SMG), sublingual (SLG), and parotid glands (PG) were dissected at day 105. Using different staining techniques, morphological, cellular, and molecular changes were investigated in the salivary glands. Results: Saliva production was significantly reduced in irradiated compared to control mice at day 35, 80, and 105. We observed a significant decrease in total gland area and a significant increase in fibrotic area in irradiated compared to control SMG at day 105. Atrophy of acinar cells was observed in all irradiated SMG and SLG. Increased amount of chronic inflammatory cells, increased cell proliferation and altered expression of apoptotic markers were found in atrophic areas of irradiated glands. Conclusion: Acinar and duct cells in irradiated salivary glands show increased cell proliferation and altered expression of apoptotic markers, proposing an attempt to overcome or withstand tissue damage caused by irradiation. This suggests a potential for regeneration of salivary glands after radiation therapy.

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Section: Discussionmentioning

confidence: 99%

Fractionated irradiation of murine salivary glands resulted in focal acinar cell atrophy, immune cell infiltration, fibrosis, and hyposalivation

Juvkam,

Zlygosteva,

Malinen

et al. 2023

Preprint

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“…Other than these elements, Bax∆2 retains the same sequence as Baxα, including the core regions for homodimerization and heterodimerization and pro-death Bcl-2 homology (BH) domains [ 11 , 12 ]. Baxα protein is ubiquitously and readily detected in most normal human organ systems [ 14 , 15 , 16 ], except for the brain [ 15 , 16 , 17 ]. In contrast, the distribution of Bax∆2 proteins in normal human tissues was found to be scattered and at lower levels [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Unconventional Source of Neurotoxic Protein Aggregation from Organelle Off-Target Bax∆2 in Alzheimer’s Disease

et al. 2023

Self Cite

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Protein aggregates are a hallmark of Alzheimer’s disease (AD). Extensive studies have focused on β-amyloid plaques and Tau tangles. Here, we illustrate a novel source of protein aggregates in AD neurons from organelle off-target proteins. Bax is a mitochondrial pore-forming pro-death protein. What happens to Bax if it fails to target mitochondria? We previously showed that a mitochondrial target-deficient alternatively spliced variant, Bax∆2, formed large cytosolic protein aggregates and triggered caspase 8-mediated cell death. Bax∆2 protein levels were low in most normal organs and the proteins were quickly degraded in cancer. Here, we found that 85% of AD patients had Bax∆2 required alternative splicing. Increased Bax∆2 proteins were mostly accumulated in neurons of AD-susceptible brain regions. Intracellularly, Bax∆2 aggregates distributed independently of Tau tangles. Interestingly, Bax∆2 aggregates triggered the formation of stress granules (SGs), a large protein-RNA complex involved in AD pathogenesis. Although the functional domains required for aggregation and cell death are the same as in cancer cells, Bax∆2 relied on SGs, not caspase 8, for neuronal cell death. These results imply that the aggregation of organelle off-target proteins, such as Bax∆2, broadens the scope of traditional AD pathogenic proteins that contribute to the neuronal stress responses and AD pathogenesis.

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Alternative production of pro-death Bax∆2 protein via ribosomal frameshift in Alzheimer’s disease

Yao,

Mañas,

Beatty

et al. 2024

Sci Rep

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Expression profile of the proapoptotic protein Bax in the human brain

Cited by 3 publications

References 56 publications

Fractionated irradiation of murine salivary glands resulted in focal acinar cell atrophy, immune cell infiltration, fibrosis, and hyposalivation

Fractionated irradiation of murine salivary glands resulted in focal acinar cell atrophy, immune cell infiltration, fibrosis, and hyposalivation

Unconventional Source of Neurotoxic Protein Aggregation from Organelle Off-Target Bax∆2 in Alzheimer’s Disease

Alternative production of pro-death Bax∆2 protein via ribosomal frameshift in Alzheimer’s disease

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