Reduction in Insulin Mediated ERK Phosphorylation by Palmitate in Liver Cells Is Independent of Fatty Acid Induced ER Stress

Mubarak, Sindiyan Alshaikh; Otaibi, Abeer Al; Qarni, Ali Al; Bakillah, Ahmed; Iqbal, Jahangir

doi:10.3390/nu14173641

Cited by 3 publications

(2 citation statements)

References 38 publications

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“…The free fatty acids elevated in patients with NASH are positively correlated with the severity of disease [ 28 ]. Saturated free fatty acids (FFAs) such as palmitate in the circulation are apt to cause endoplasmic reticulum (ER) stress, apoptosis and insulin-resistance in peripheral tissues [ 29 , 30 , 31 ]. Figure 4 , in reality, was mimicking such a condition ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

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Inhibitory Effect of Styrylpyrone Extract of Phellinus linteus on Hepatic Steatosis in HepG2 Cells

Chiu

Chen

Lieu

et al. 2023

IJMS

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The prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be approximately about 25.24% of the population worldwide. NAFLD is a complex syndrome and is characterized by a simple benign hepatocyte steatosis to more severe steatohepatitis in the liver pathology. Phellinus linteus (PL) is traditionally used as a hepatoprotective supplement. Styrylpyrone-enriched extract (SPEE) obtained from the PL mycelia has been shown to have potential inhibition effects on high-fat- and high-fructose-diet-induced NAFLD. In the continuous study, we aimed to explore the inhibitory effects of SPEE on free fatty acid mixture O/P [oleic acid (OA): palmitic acid (PA); 2:1, molar ratio]-induced lipid accumulation in HepG2 cells. Results showed that SPEE presented the highest free radical scavenging ability on DPPH and ABTS, and reducing power on ferric ions, better than that of partitions obtained from n-hexane, n-butanol and distilled water. In free-fatty-acid-induced lipid accumulation in HepG2 cells, SPEE showed an inhibition effect on O/P-induced lipid accumulation of 27% at a dosage of 500 μg/mL. As compared to the O/P induction group, the antioxidant activities of superoxide dismutase, glutathione peroxidase and catalase were enhanced by 73%, 67% and 35%, respectively, in the SPEE group. In addition, the inflammatory factors (TNF-α, IL-6 and IL-1β) were significantly down-regulated by the SPEE treatment. The expressions of anti-adipogenic genes involved in hepatic lipid metabolism of 5’ adenosine monophosphate (AMP)-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were enhanced in the SPEE supplemented HepG2 cells. In the protein expression study, p-AMPK, SIRT1 and PGC1-α were significantly increased to 121, 72 and 62%, respectively, after the treatment of SPEE. Conclusively, the styrylpyrone-enriched extract SPEE can ameliorate lipid accumulation and decrease inflammation and oxidative stress through the activation of SIRT1/AMPK/PGC1-α pathways.

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Section: Discussionmentioning

confidence: 99%

“…Figure 4 , in reality, was mimicking such a condition ( Figure 4 ). ER stress refers to an imbalance between the demand for protein folding and the protein folding capacity of the ER [ 29 ]. Previous studies indicate that the antioxidant resveratrol, a SIRT1 activator, significantly inhibits palmitate-induced ER stress [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effect of Styrylpyrone Extract of Phellinus linteus on Hepatic Steatosis in HepG2 Cells

Chiu

Chen

Lieu

et al. 2023

IJMS

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Emerging role and therapeutic implications of p53 in intervertebral disc degeneration

Wang,

Hu,

Zhang

et al. 2023

Cell Death Discov.

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Lower back pain (LBP) is a common degenerative musculoskeletal disease that imposes a huge economic burden on both individuals and society. With the aggravation of social aging, the incidence of LBP has increased globally. Intervertebral disc degeneration (IDD) is the primary cause of LBP. Currently, IDD treatment strategies include physiotherapy, medication, and surgery; however, none can address the root cause by ending the degeneration of intervertebral discs (IVDs). However, in recent years, targeted therapy based on specific molecules has brought hope for treating IDD. The tumor suppressor gene p53 produces a transcription factor that regulates cell metabolism and survival. Recently, p53 was shown to play an important role in maintaining IVD microenvironment homeostasis by regulating IVD cell senescence, apoptosis, and metabolism by activating downstream target genes. This study reviews research progress regarding the potential role of p53 in IDD and discusses the challenges of targeting p53 in the treatment of IDD. This review will help to elucidate the pathogenesis of IDD and provide insights for the future development of precision treatments.

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Thapsigargin and Tunicamycin Block SARS-CoV-2 Entry into Host Cells via Differential Modulation of Unfolded Protein Response (UPR), AKT Signaling, and Apoptosis

Al Otaibi,

Al Shaikh Mubarak,

Al Hejji

et al. 2024

Cells

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Background: SARS-Co-V2 infection can induce ER stress-associated activation of unfolded protein response (UPR) in host cells, which may contribute to the pathogenesis of COVID-19. To understand the complex interplay between SARS-Co-V2 infection and UPR signaling, we examined the effects of acute pre-existing ER stress on SARS-Co-V2 infectivity. Methods: Huh-7 cells were treated with Tunicamycin (TUN) and Thapsigargin (THA) prior to SARS-CoV-2pp transduction (48h p.i.) to induce ER stress. Pseudo-typed particles (SARS-CoV-2pp) entry into host cells was measured by Bright GloTM luciferase assay. Cell viability was assessed by cell titer Glo® luminescent assay. The mRNA and protein expression was evaluated by RT-qPCR and Western Blot. Results: TUN (5 µg/ml) and THA (1 µM) efficiently inhibited the entry of SARS-CoV-2pp into host cells without any cytotoxic effect. TUN and THA's attenuation of virus entry was associated with differential modulation of ACE2 expression. Both TUN and THA significantly reduced the expression of stress-inducible ER chaperone GRP78/BiP in transduced cells. In contrast, the IRE1-XBP1s and PERK-eIF2α-ATF4-CHOP signaling pathways were downregulated with THA treatment, but not TUN in transduced cells. Insulin-mediated glucose uptake and phosphorylation of Ser307 IRS-1 and downstream p-AKT were enhanced with THA in transduced cells. Furthermore, TUN and THA differentially affected lipid metabolism and apoptotic signaling pathways. Conclusions: These findings suggest that short-term pre-existing ER stress prior to virus infection induces a specific UPR response in host cells capable of counteracting stress-inducible elements signaling, thereby depriving SARS-Co-V2 of essential components for entry and replication. Pharmacological manipulation of ER stress in host cells might provide new therapeutic strategies to alleviate SARS-CoV-2 infection.

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Reduction in Insulin Mediated ERK Phosphorylation by Palmitate in Liver Cells Is Independent of Fatty Acid Induced ER Stress

Cited by 3 publications

References 38 publications

Inhibitory Effect of Styrylpyrone Extract of Phellinus linteus on Hepatic Steatosis in HepG2 Cells

Inhibitory Effect of Styrylpyrone Extract of Phellinus linteus on Hepatic Steatosis in HepG2 Cells

Emerging role and therapeutic implications of p53 in intervertebral disc degeneration

Thapsigargin and Tunicamycin Block SARS-CoV-2 Entry into Host Cells via Differential Modulation of Unfolded Protein Response (UPR), AKT Signaling, and Apoptosis

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