Palmitic acid induces human osteoblast-like Saos-2 cell apoptosis via endoplasmic reticulum stress and autophagy

Yang, Lei; Guan, Gaopeng; Lei, Lanjie; Lv, Qizhuang; Liu, Shengyuan; Zhan, Xiaoyun; Jiang, Zhenzhen; Gu, Xiang

doi:10.1007/s12192-018-0936-8

Cited by 66 publications

(40 citation statements)

References 63 publications

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“…GRP78 is an ER stress-response protein, and its expression is a typical marker of ER stress activation. Our previous results showed that PA triggers ER stress and then induces apoptosis though CHOP activation in Saos-2 cells [18]. In addition, this result is consistent with the results of other studies that showed that PA induces ER stress and apoptosis in hepatoma cells [35] and myocardial cells [34].…”

Section: Discussionsupporting

confidence: 91%

“…The cells were analyzed using a fluorescence-activated cell sorter (Becton, Dickinson and Company, USA) within 1 h of staining. The proportion of early apoptotic cells was determined by measuring the percentage of Annexin V+/PI− cells; the proportion of progressed apoptotic cells was obtained by determining the percentage of Annexin V+/PI+ cells; the proportion of necrotic cells was detected by determining the percentage of Annexin V−/PI+ cells and Annexin V−/PI− cells were considered surviving cells as previously reported [18].…”

Section: Methodsmentioning

confidence: 99%

“…The primary objective of the UPR is to re-establish homeostasis and alleviate ER stress by increasing the protein folding capacity and decreasing the unfolded protein load. However, when ER stress fails to manage misfolded and unfolded proteins, cell apoptosis is induced [18]. Previous studies have reported that melatonin inhibits cell apoptosis by attenuating ER stress [19–21].…”

Section: Introductionmentioning

confidence: 99%

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Melatonin attenuates palmitic acid-induced mouse granulosa cells apoptosis via endoplasmic reticulum stress

et al. 2019

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Background Palmitic acid (PA), the main component of dietary saturated fat, causes apoptosis in many cell types, including mouse granulosa cell. Melatonin, an important endogenous hormone, has beneficial effects on female reproductive processes. Since elevated PA levels are present in follicular fluid (FF) of patients with infertility and are shown to be toxic for granulosa cells, we investigated the molecular mechanisms of PA toxicity in mouse granulosa cells and explored the effects of melatonin on PA-induced apoptosis. Methods Granulosa cells from immature female mice were cultured for 24 h in medium containing PA and/or melatonin. Then, the effects of PA alone or combined with melatonin on viability, apoptosis and endoplasmic reticulum (ER) stress in granulosa cells were detected by methyl thiazolyl tetrazolium (MTT) assay, flow cytometry assay and western blot. After 48 h of PA and/or melatonin treatment, the concentrations of estradiol (E2) and progesterone (P4) in the culture supernatants were measured with ELISA kits. Results In this study, we explored the effects of melatonin on cell viability and apoptosis in PA-treated mouse granulosa cells and uncovered the signaling pathways involved in these processes. Our results showed that 200-800 μM PA treatment reduces cell viability, induces cell apoptosis, enhances the expression of apoptosis-related genes (Caspase 3 and B-cell lymphoma-2 (BCL-2) associated X protein (BAX)), and activates the expression of ER stress marker genes (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)). Melatonin treatment (1-10 μM) suppresses 400 μM PA-induced cell viability decrease, cell apoptosis, Caspase 3 activation, and BAX, CHOP, and GRP78 expression. In addition, we found that 10 μM melatonin successfully attenuated the 400 μM PA-induced estrogen (E2) and progesterone (P4) decreases. Conclusions This study suggests that PA triggers cell apoptosis via ER stress and that melatonin protects cells against apoptosis by inhibiting ER stress in mouse granulosa cells. Electronic supplementary material The online version of this article (10.1186/s13048-019-0519-z) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Melatonin attenuates palmitic acid-induced mouse granulosa cells apoptosis via endoplasmic reticulum stress

et al. 2019

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“…Numerous studies have suggested that increased ROS activate various signaling pathways, resulting in DNA damage and apoptosis [13,14]. Previous studies have also shown that oxidative and ER stresses are closely related [15,16]. Both oxidative stress [21] and ER stress [9] are involved in PA-induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Oxidative and endoplasmic reticulum stresses are involved in palmitic acid-induced H9c2 cell apoptosis

et al. 2019

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Palmitic acid (PA) is the most common saturated long-chain fatty acid that causes damage to heart muscle cells. However, the molecular mechanism of PA toxicity in myocardial cells is not fully understood. In the present study, we explored the effects of PA on proliferation and apoptosis of H9c2 cardiomyocytes, and uncovered the signaling pathways involved in PA toxicity. Our study revealed induction of both oxidative and endoplasmic reticulum (ER) stresses and exacerbation of apoptosis in PA-treated H9c2 cells. Inhibition of oxidative stress by N-acetylcysteine (NAC) reduced apoptosis and decreased ER stress in PA-treated H9c2 cells. Moreover, inhibition of ER stress by 4-phenyl butyric acid decreased apoptosis and attenuated oxidative stress. In summary, the present study demonstrated that oxidative stress coordinates with ER stress to play important roles in PA-induced H9c2 cell apoptosis.

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“…To dissect the effects of altered lipid metabolism from other metabolic derangements in these models, in vitro culture systems wherein cultures of primary osteoblasts or osteoblast-like cell lines are treated with exogenous lipids have proven helpful (124,(135)(136)(137)(138)(139). The common finding in these studies is that the exposure to sufficient quantities of cholesterol, palmitate or oxidized LDL [a product of LDL interaction with reactive oxygen species (140)] reduces the proliferation of osteoblastic cells, induces cell death, and impairs osteoblast differentiation.…”

Section: Effect Of Dyslipidemia On Bone Structure and Remodelingmentioning

confidence: 99%

Dual Effects of Lipid Metabolism on Osteoblast Function

2020

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The skeleton is a dynamic and metabolically active organ with the capacity to influence whole body metabolism. This newly recognized function has propagated interest in the connection between bone health and metabolic dysfunction. Osteoblasts, the specialized mesenchymal cells responsible for the production of bone matrix and mineralization, rely on multiple fuel sources. The utilization of glucose by osteoblasts has long been a focus of research, however, lipids and their derivatives, are increasingly recognized as a vital energy source. Osteoblasts possess the necessary receptors and catabolic enzymes for internalization and utilization of circulating lipids. Disruption of these processes can impair osteoblast function, resulting in skeletal deficits while simultaneously altering whole body lipid homeostasis. This article provides an overview of the metabolism of postprandial and stored lipids and the osteoblast's ability to acquire and utilize these molecules. We focus on the requirement for fatty acid oxidation and the pathways regulating this function as well as the negative impact of dyslipidemia on the osteoblast and skeletal health. These findings provide key insights into the nuances of lipid metabolism in influencing skeletal homeostasis which are critical to appreciate the extent of the osteoblast's role in metabolic homeostasis.

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Palmitic acid induces human osteoblast-like Saos-2 cell apoptosis via endoplasmic reticulum stress and autophagy

Cited by 66 publications

References 63 publications

Melatonin attenuates palmitic acid-induced mouse granulosa cells apoptosis via endoplasmic reticulum stress

Melatonin attenuates palmitic acid-induced mouse granulosa cells apoptosis via endoplasmic reticulum stress

Oxidative and endoplasmic reticulum stresses are involved in palmitic acid-induced H9c2 cell apoptosis

Dual Effects of Lipid Metabolism on Osteoblast Function

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