Hydronidone induces apoptosis in activated hepatic stellate cells through endoplasmic reticulum stress‐associated mitochondrial apoptotic pathway

Journal of Gastroenterology and Hepatology, Год журнала: 2024, Номер 39(8), С. 1695 - 1703

Опубликована: Май 28, 2024

Abstract Background and Aim Hydronidone (HDD) is a novel pirfenidone derivative developed initially to reduce hepatotoxicity. Our previous studies in animals humans have demonstrated that HDD treatment effectively attenuates liver fibrosis, yet the underlying mechanism remains unclear. This study aimed investigate whether exerts its anti‐fibrotic effect by inducing apoptosis activated hepatic stellate cells (aHSCs) through endoplasmic reticulum stress (ERS)‐associated mitochondrial apoptotic pathway. Methods The carbon tetrachloride (CCl 4 )‐ 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC)‐induced fibrosis models were used for vivo studies. In vitro conducted using human cell line LX‐2. of on aHSCs was examined TUNEL flow cytometry assays. small interfering RNA (siRNA) technique employed downregulate expression interest genes. Results significantly promoted both CCl ‐ DDC‐induced mice LX‐2 cells. Mechanistic revealed triggered ERS subsequently IRE1α‐ASK1‐JNK Furthermore, influx cytochrome c from mitochondria into cytoplasm increased, leading dysfunction ultimately triggering aHSCs. Notably, inhibition IRE1α or ASK1 siRNA partially abrogated pro‐apoptotic Conclusions findings suggest induces via ERS‐associated pathway, potentially contributing amelioration fibrosis.

Язык: Английский

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PANoptosis: Novel insight into regulated cell death and its potential role in cardiovascular diseases (Review)

International Journal of Molecular Medicine, Год журнала: 2024, Номер 54(3)

Опубликована: Июль 4, 2024

PANoptosis, a complex form of proinflammatory programmed cell death, including apoptosis, pyroptosis and necroptosis, has been an emerging concept in recent years that widely reported cancer, infectious diseases neurological disorders. Cardiovascular (CVDs) are important global health problem, posing serious threat to individuals' lives. An increasing body research shows inflammation pivotal role CVDs, which provides theoretical basis for PANoptosis promote the progression CVDs. To date, only sporadic studies on CVDs have its field not fully explored. Elucidating various modes cardiomyocyte specific molecular mechanisms links among death under stressful stimuli is notable clinical significance deeper understanding pathophysiology The present review summarizes pyroptosis, necroptosis their prospects

Язык: Английский

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Melatonin regulates endoplasmic reticulum stress in diverse pathophysiological contexts: A comprehensive mechanistic review

Journal of Cellular Physiology, Год журнала: 2024, Номер 239(11)

Опубликована: Июль 22, 2024

The endoplasmic reticulum (ER) is crucial for protein quality control, and disruptions in its function can lead to various diseases. ER stress triggers an adaptive response called the unfolded (UPR), which either restore cellular homeostasis or induce cell death. Melatonin, a safe multifunctional compound, shows promise controlling could be valuable therapeutic agent managing UPR. By regulating mitochondrial functions, melatonin helps maintain via reduction of oxidative stress, inflammation, apoptosis. Melatonin directly indirectly interfere with ER-associated sensors downstream targets UPR, impacting death, autophagy, molecular repair, among others. Crucially, this review explores mechanistic role on diseases including liver damage, neurodegeneration, reproductive disorders, pulmonary disease, cardiomyopathy, insulin resistance, renal dysfunction, cancer. Interestingly, while it alleviates burden most pathological contexts, paradoxically stimulate cancer cells, highlighting intricate involvement homeostasis. With numerous successful studies using vivo vitro models, continuation clinical trials imperative fully explore melatonin's potential these conditions.

Язык: Английский

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Regulation mechanism of endoplasmic reticulum stress on metabolic enzymes in liver diseases

Pharmacological Research, Год журнала: 2024, Номер 207, С. 107332 - 107332

Опубликована: Июль 30, 2024

The endoplasmic reticulum (ER) plays a pivotal role in protein folding and secretion, Ca

Язык: Английский

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Endoplasmic reticulum stress in liver fibrosis: Mechanisms and therapeutic potential

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер unknown, С. 167695 - 167695

Опубликована: Янв. 1, 2025

Язык: Английский

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