Selenium-enriched Spirulina protects INS-1E pancreatic beta cells from human islet amyloid polypeptide-induced apoptosis through suppression of ROS-mediated mitochondrial dysfunction and PI3/AKT pathway

Li, Xiaoling; Wong, Yum-Shing; Xu, Gang; Chan, Juliana C.N.

doi:10.1007/s00394-014-0732-x

Cited by 26 publications

(14 citation statements)

References 50 publications

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“…After entering into the hepatocytes, a portion of Cu is being transported to the mitochondria for cytochrome c oxidase incorporation [40]. High levels of Cu can induce the overproduction of ROS [3], which further impairs mitochondrial electron transport and results in mitochondrial dysfunction that is linked to the occurrence of apoptosis [41]. In this study, the rates of apoptotic hepatocytes were higher in the three Cu treatment groups than in the control group.…”

Section: Discussionmentioning

confidence: 55%

Copper Induces Oxidative Stress and Apoptosis in the Mouse Liver

Liu

Guo

Jian

et al. 2020

Oxidative Medicine and Cellular Longevity

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Copper (Cu) is an essential trace element involved in the normal physiological processes of animals. However, excessive exposure to Cu can produce numerous detrimental impacts. The aim of this study was to investigate the effects of Cu on oxidative stress and apoptosis as well as their relationship in the mouse liver. Four-week-old ICR mice (n=240) were randomly assigned to different Cu (Cu2+-CuSO4) treatment groups (0, 4, 8, and 16 mg/kg) for periods of 21 and 42 days. The high doses of Cu exposure could induce oxidative stress, by increasing the levels of reactive oxygen species (ROS) and protein carbonyls (PC) and decreasing the activities of antisuperoxide anion (ASA) and antihydroxyl radical (AHR) and content of glutathione (GSH), as well as activities and mRNA expression levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Moreover, high doses of Cu exposure induced hepatic apoptosis via the mitochondrial apoptotic pathway, as characterized by the depolarization of mitochondrial membrane potential (MMP); significantly increased mRNA and protein expression levels of cytosolic cytochrome (Cyt c), apoptosis-inducing factor (AIF), endonuclease G (Endo G), apoptosis protease-activating factor-1 (Apaf-1), cleaved caspase-9, cleaved caspase-3, cleaved PARP, Bcl-2 antagonist killer (Bak), Bcl-2-associated X protein (Bax), and Bcl-2-interacting mediator of cell death (Bim); and decreased mRNA and protein expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-extra-large (Bcl-xL). Furthermore, the activation of the tumor necrosis factor receptor-1 (TNF-R1) signaling pathway was involved in Cu-induced apoptosis, as characterized by the significantly increased mRNA and protein expression levels of TNF-R1, Fas-associated death domain (FADD), TNFR-associated death domain (TRADD), and cleaved caspase-8. These results indicated that exposure to excess Cu could cause oxidative stress triggered by ROS overproduction and diminished antioxidant function, which in turn promoted hepatic apoptosis via mitochondrial apoptosis and that the TNF-R1 signaling pathway was also involved in the Cu-induced apoptosis.

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Section: Discussionmentioning

confidence: 55%

Copper Induces Oxidative Stress and Apoptosis in the Mouse Liver

Liu

Guo

Jian

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…In addition, the overexpression of MKP-5 inhibited the PA-induced production of intracellular ROS and its associated genes, P22phox and Nox-4. One recent study found that ROS are able to inhibit PI3K/AKT insulin signaling and mitochondrial function, inducing the apoptosis of islet β-cells [ 54 ]. Similarly, MKP-5 may impair the release of inflammatory factors and the production of ROS, thereby reducing the apoptosis and dysfunction of islet cells under lipotoxic conditions.…”

Section: Discussionmentioning

confidence: 99%

MKP-5 Relieves Lipotoxicity-Induced Islet β-Cell Dysfunction and Apoptosis via Regulation of Autophagy

Zhao

et al. 2020

IJMS

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Mitogen-activated protein kinase phosphatase-5 (MKP-5) is a regulator of extracellular signaling that is known to regulate lipid metabolism. In this study, we found that obesity caused by a high-fat diet (HFD) decreased the expression of MKP-5 in the pancreas and primary islet cells derived from mice. Then, we further investigated the role of MKP-5 in the protection of islet cells from lipotoxicity by modulating MKP-5 expression. As a critical inducer of lipotoxicity, palmitic acid (PA) was used to treat islet β-cells. We found that MKP-5 overexpression restored PA-mediated autophagy inhibition in Rin-m5f cells and protected these cells from PA-induced apoptosis and dysfunction. Consistently, a lack of MKP-5 aggravated the adverse effects of lipotoxicity. Islet cells from HFD-fed mice were infected using recombinant adenovirus expressing MKP-5 (Ad-MKP-5), and we found that Ad-MKP-5 was able to alleviate HFD-induced apoptotic protein activation and relieve the HFD-mediated inhibition of functional proteins. Notably, HFD-mediated impairments in autophagic flux were restored by Ad-MKP-5 transduction. Furthermore, the autophagy inhibitor 3-methyladenine (3-MA) was used to treat Rin-m5f cells, confirming that the MKP-5 overexpression suppressed apoptosis, dysfunction, inflammatory response, and oxidative stress induced by PA via improving autophagic signaling. Lastly, employing c-Jun amino-terminal kinas (JNK), P38, or extracellular-regulated kinase (ERK) inhibitors, we established that the JNK and P38 MAPK pathways were involved in the MKP-5-mediated apoptosis, dysfunction, and autophagic inhibition observed in islet β cells in response to lipotoxicity.

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“…The normalizing effects by Spirulina on IL-1β, Nrf2 and γGCLC levels in our study can be exerted by different mechanisms. The protective effects in vivo are generally attributed to the anti-oxidant and free radical scavenging properties of the active ingredient C-phycocyanin [36] Concerning mechanistic studies in vitro Spirulina components have also been shown to reactivate the kinase Akt [37], [38] decrease the expression of HDACs, restore LPS mediated decreases in acetylated levels of histone H3 [39], down-regulate pp38 and upregulate ERK1/2 [40]. In our earlier studies in vitro we showed that active p38 had negative and that ERK1/2 had positive effects of Nrf2 activation [28].…”

Section: Discussionmentioning

confidence: 99%

Spirulinadiet to lactating mothers protects the antioxidant system and reduces inflammation in post-natal brain after systemic inflammation

Patil

Matte

Mallard

et al. 2016

Nutritional Neuroscience

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Selenium-enriched Spirulina protects INS-1E pancreatic beta cells from human islet amyloid polypeptide-induced apoptosis through suppression of ROS-mediated mitochondrial dysfunction and PI3/AKT pathway

Abstract: Our results showed that Se-SE protects INS-1E cells from hIAPP-induced cell death through preventing ROS overproduction, mitochondrial dysfunction and modulating PI3K/AKT pathway.

Cited by 26 publications

References 50 publications

Copper Induces Oxidative Stress and Apoptosis in the Mouse Liver

Copper Induces Oxidative Stress and Apoptosis in the Mouse Liver

MKP-5 Relieves Lipotoxicity-Induced Islet β-Cell Dysfunction and Apoptosis via Regulation of Autophagy

Spirulinadiet to lactating mothers protects the antioxidant system and reduces inflammation in post-natal brain after systemic inflammation

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