Gut microbiota dependent trimethylamine N-oxide aggravates angiotensin II–induced hypertension

Redox Biology, Год журнала: 2021, Номер 46, С. 102115 - 102115

Опубликована: Авг. 25, 2021

Gut microbiota produce Trimethylamine N-oxide (TMAO) by metabolizing dietary phosphatidylcholine, choline, l-carnitine and betaine. TMAO is implicated in the pathogenesis of chronic kidney disease (CKD), diabetes, obesity atherosclerosis. We test, whether augments angiotensin II (Ang II)-induced vasoconstriction hence promotes Ang II-induced hypertension. Plasma levels were indeed elevated hypertensive patients, thus potential pathways which mediates these effects explored. (400 ng/kg-1min-1) was chronically infused for 14 days via osmotic minipumps C57Bl/6 mice. (1%) or antibiotics given drinking water. Vasoconstriction renal afferent arterioles mesenteric arteries assessed microperfusion wire myograph, respectively. In mice, systolic blood pressure caused vasoconstriction, alleviated antibiotics. enhanced acute pressor responses (12.2 ± 1.9 versus 20.6 1.4 mmHg; P < 0.05) (32.3 2.6 55.9 7.0%, 0.001). intracellular Ca2+ release (147 7 234 26%; 0.001) mouse vascular smooth muscle cells (VSMC, 123 3 157 9%; increased treatment. Preincubation VSMC with activated PERK/ROS/CaMKII/PLCβ3 pathway. Pharmacological inhibition PERK, ROS, CaMKII PLCβ3 impaired effect on release. Thus, facilitates thereby promoting hypertension, involves axis.

Язык: Английский

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Diversity and complexity of cell death: a historical review

Experimental & Molecular Medicine, Год журнала: 2023, Номер 55(8), С. 1573 - 1594

Опубликована: Авг. 23, 2023

Abstract Death is the inevitable fate of all living organisms, whether at individual or cellular level. For a long time, cell death was believed to be an undesirable but unavoidable final outcome nonfunctioning cells, as inflammation inevitably triggered in response damage. However, experimental evidence accumulated over past few decades has revealed different types that are genetically programmed eliminate unnecessary severely damaged cells may damage surrounding tissues. Several death, including apoptosis, necrosis, autophagic and lysosomal which classified pyroptosis, necroptosis, NETosis, inflammatory have been described years. Recently, several novel forms namely, mitoptosis, paraptosis, immunogenic entosis, methuosis, parthanatos, ferroptosis, autosis, alkaliptosis, oxeiptosis, cuproptosis, erebosis, discovered advanced our understanding its complexity. In this review, we provide historical overview discovery characterization highlight their diversity We also briefly discuss regulatory mechanisms underlying each type implications various physiological pathological contexts. This review provides comprehensive can leveraged develop therapeutic strategies for diseases.

Язык: Английский

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Excessive Apoptosis in Ulcerative Colitis: Crosstalk Between Apoptosis, ROS, ER Stress, and Intestinal Homeostasis

Inflammatory Bowel Diseases, Год журнала: 2021, Номер 28(4), С. 639 - 648

Опубликована: Дек. 6, 2021

Abstract Ulcerative colitis (UC), an etiologically complicated and relapsing gastrointestinal disease, is characterized by the damage of mucosal epithelium destruction intestinal homeostasis, which has caused a huge social economic burden on health system all over world. Its pathogenesis multifactorial, including environmental factors, genetic susceptibility, epithelial barrier defect, symbiotic flora imbalance, dysregulated immune response. Thus far, although cells have become focus most research, it increasingly clear that play important role in progression UC. Notably, apoptosis vital catabolic process cells, crucial to maintain stability environment regulate ecology. In this review, mechanism induced reactive oxygen species endoplasmic reticulum stress, as well excessive dysfunction gut microbiology imbalance are systematically comprehensively summarized. Further understanding UC may provide novel strategy for its therapy clinical practices development new drugs.

Язык: Английский

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Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons

Journal of Experimental & Clinical Cancer Research, Год журнала: 2021, Номер 40(1)

Опубликована: Янв. 11, 2021

Abstract Solid tumors often grow in a micro-environment characterized by < 2% O 2 tension. This condition, together with the aberrant activation of specific oncogenic patwhays, increases amount and activity hypoxia-inducible factor-1α (HIF-1α), transcription factor that controls up to 200 genes involved neoangiogenesis, metabolic rewiring, invasion drug resistance. Hypoxia also induces endoplasmic reticulum (ER) stress, condition triggers cell death, if cells are irreversibly damaged, or survival, stress is mild. chronic ER both induce chemoresistance. In this review we discuss multiple interconnected circuitries link hypoxic environment, We suggest hypoxia train select more adapted survive unfavorable conditions, activating pleiotropic mechanisms including apoptosis inhibition, anti-oxidant defences, drugs efflux. adaptative process unequivocally expands clones acquire resistance chemotherapy. believe pharmacological inhibitors HIF-1α modulators although low specificty anti-cancer efficacy when used as single agents, may be repurposed chemosensitizers against chemorefractory next future.

Язык: Английский

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Molecular responses to acute exercise and their relevance for adaptations in skeletal muscle to exercise training

Physiological Reviews, Год журнала: 2022, Номер 103(3), С. 2057 - 2170

Опубликована: Ноя. 17, 2022

Repeated, episodic bouts of skeletal muscle contraction undertaken frequently as structured exercise training are a potent stimulus for physiological adaptation in many organs. Specifically, muscle, remarkable plasticity is demonstrated by the remodeling structure and function terms muscular size, force, endurance, contractile velocity result functional demands induced various types training. This plasticity, mechanistic basis adaptations to response training, underpinned activation and/or repression molecular pathways processes each individual acute session. These include transduction signals arising from neuronal, mechanical, metabolic, hormonal stimuli through complex signal networks, which linked myriad effector proteins involved regulation pre- posttranscriptional processes, protein translation degradation processes. review therefore describes exercise-induced responses including emerging concepts such epigenetic degradation. A critical appraisal methodological approaches current state knowledge informs series recommendations offered future directions field.

Язык: Английский

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