BOK Is a Non-canonical BCL-2 Family Effector of Apoptosis Regulated by ER-Associated Degradation

Cell, Год журнала: 2016, Номер 165(2), С. 421 - 433

Опубликована: Март 5, 2016

Язык: Английский

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Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer

Nature reviews. Cancer, Год журнала: 2022, Номер 22(6), С. 323 - 339

Опубликована: Март 9, 2022

Язык: Английский

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Mitophagy regulates mitochondrial network signaling, oxidative stress, and apoptosis during myoblast differentiation

Autophagy, Год журнала: 2019, Номер 15(9), С. 1606 - 1619

Опубликована: Март 12, 2019

Macroautophagy/autophagy is a degradative process essential for various cellular processes. We previously demonstrated that autophagy-deficiency causes myoblast apoptosis and impairs myotube formation. In this study, we continued work with particular emphasis on mitochondrial remodelling stress/apoptotic signaling. found increased (p < 0.05) autophagic (e.g., altered LC3B levels, ATG7, decreased SQSTM1) mitophagic BNIP3 upregulation, localized GFP-LC3 puncta, elevated LC3B-II) signaling during differentiation. shRNA-mediated knockdown of ATG7 (shAtg7) these responses, while increasing CASP3 activity ANXA5/annexin V staining in differentiating myoblasts; ultimately resulting dramatically impaired myogenesis. Further confirming the importance mitophagy CRISPR-Cas9-mediated knockout Bnip3 (bnip3-/-) resulted DNA fragmentation as well addition, shAtg7 myoblasts displayed greater endoplasmic reticulum CAPN HSPA) mPTP formation, reduced membrane potential, 4-HNE) stress. bnip3-/- also mitochondria-associated PPARGC1A, DNM1L, OPA1) protein content SLC25A4, VDAC1, CYCS). Moreover, CYCS AIFM1 release from mitochondria, CASP9 activation. Similarly, had significantly higher activation Importantly, administration chemical inhibitor (Ac-LEHD-CHO) or dominant-negative (ad-DNCASP9) partially recovered differentiation myogenesis myoblasts. Together, data demonstrate an role autophagy protecting oxidative stress apoptotic differentiation, regulation network Abbreviations: 3MA: 3-methyladenine; 4-HNE: 4-hydroxynonenal; ACT: actin; AIFM1/AIF: apoptosis-inducing factor, mitochondrion-associated 1; ANXA5: annexin V; ATG7: related 7; AU: arbitrary units; BAX: BCL2-associated X protein; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1, related; BNIP3: BCL2/adenovirus E1B interacting 3; CAPN: calpain; CASP: caspase; CASP3: caspase CASP8: 8; CASP9: 9; CASP12: 12; CAT: catalase; CQ: chloroquine; CYCS: cytochrome c, somatic; DCF; 2',7'-dichlorofluorescein; DNM1L/DRP1: dynamin 1-like; DM: media; DMEM: Dulbecco's modified Eagle's medium; ER: reticulum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent GM: growth p-H2AFX: phosphorylated H2A histone family, member X; H2BFM: H2B M; HBSS: Hanks balanced salt solution; HSPA/HSP70: heat shock family A; JC-1: tetraethylbenzimidazolylcarbocyanine iodide; MAP1LC3B/LC3B: microtubule-associated 1 light chain 3 beta; mPTP: permeability transition pore; MYH: myosin heavy chain; MYOG: myogenin; OPA1: OPA1, like GTPase; PI: propidium PINK1: PTEN induced putative kinase PPARGC1A/PGC1α: peroxisome proliferative activated receptor, gamma, coactivator alpha; ROS: reactive oxygen species; SLC25A4/ANT1: solute carrier 25 (mitochondrial carrier, adenine nucleotide translocator), 4; SOD1: superoxide dismutase soluble; SOD2: 2, mitochondrial; SQSTM1/p62: sequestosome VDAC1: voltage-dependent anion channel 1.

Язык: Английский

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The regulation of autophagy by calcium signals: Do we have a consensus?

Cell Calcium, Год журнала: 2017, Номер 70, С. 32 - 46

Опубликована: Авг. 19, 2017

Язык: Английский

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The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer

Cells, Год журнала: 2019, Номер 8(9), С. 1055 - 1055

Опубликована: Сен. 8, 2019

The generation of reducing equivalent NADPH via glucose-6-phosphate dehydrogenase (G6PD) is critical for the maintenance redox homeostasis and reductive biosynthesis in cells. also plays key roles cellular processes mediated by signaling. Insufficient G6PD activity predisposes cells to growth retardation demise. Severely lacking impairs embryonic development delays organismal growth. Altered associated with pathophysiology, such as autophagy, insulin resistance, infection, inflammation, well diabetes hypertension. Aberrant activation leads enhanced cell proliferation adaptation many types cancers. present review aims update existing knowledge concerning emphasizes how modulates signaling affects survival demise, particularly diseases cancer. Exploiting a potential drug target against cancer discussed.

Язык: Английский

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