Insulin-like growth factor-1 protects against prion peptide-induced cell death in neuronal cells via inhibition of Bax translocation

Park, Yang-Gyu; Jeong, Jae‐Kyo; Moon, Myung‐Hee; Lee, You-Jin; Seol, Jae‐Won; Kim, Shang-Jin; Kang, Seog‐Jin; Park, Sang-Youel

doi:10.3892/ijmm.2012.1087

Cited by 15 publications

(10 citation statements)

References 31 publications

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“…2A ) and Ser478 ( Fig. 2B ), as previously reported ( 29 ). Since Akt is activated via the PI3K/PDK1 pathway ( 30 ), we further determined this signaling pathway was involved in IGF-1-induced Akt activation.…”

Section: Resultssupporting

confidence: 89%

IGF-1 protects SH-SY5Y cells against MPP+-induced apoptosis via PI3K/PDK-1/Akt pathway

Kim

Park

2018

Endocrine Connections

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Insulin-like growth factor (IGF)-1 is a well-known anti-apoptotic pro-survival factor and phosphatidylinositol-3-kinase (PI3K)/Akt pathway is linked to cell survival induced by IGF-1. It is also reported that Akt signaling is modulated by 3-phosphoinositide-dependent kinase-1 (PDK1). In the current study, we investigated whether the anti-apoptotic effect of IGF-1 in SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP+) is associated with the activity of PI3K/PDK1/Akt pathway. Treatment of cells with IGF-1 inhibited MPP+-induced apoptotic cell death. IGF-1-induced activation of Akt and the protective effect of IGF-1 on MPP+-induced apoptosis were abolished by chemical inhibition of PDK1 (GSK2334470) or PI3K (LY294002). The phosphorylated levels of Akt and PDK1 were significantly suppressed after MPP+ exposure, while IGF-1 treatment completely restored MPP+-induced reductions in phosphorylation. IGF-1 protected cells from MPP+ insult by suppressing intracellular reactive oxygen species (ROS) production and malondialdehyde levels and increasing superoxide dismutase activity. Mitochondrial ROS levels were also increased during MPP+ exposure, which were attenuated by IGF-1 treatment. In addition, IGF-1-treated cells showed increased activities of succinate dehydrogenase and citrate synthase, stabilization of mitochondrial transmembrane potential, increased ratio of Bcl-2 to Bax, prevention of cytochrome c release and inhibition of caspase-3 activation with PARP cleavage. Furthermore, the protective effects of IGF-1 on oxidative stress and mitochondrial dysfunction were attenuated when cells were preincubated with GSK2334470 or LY294002. Our data suggest that IGF-1 protects SH-SY5Y cells against MPP+-associated oxidative stress by preserving mitochondrial integrity and inhibiting mitochondrial apoptotic cascades via the activation of PI3K/PDK1/Akt pathway.

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Section: Resultssupporting

confidence: 89%

IGF-1 protects SH-SY5Y cells against MPP+-induced apoptosis via PI3K/PDK-1/Akt pathway

Kim

Park

2018

Endocrine Connections

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“…mice (Pi et al, 2007;Zhang et al, 2012). In neuronal cells, IGF1 protects against prion diseases caused by mitochondrial dysfunction and increased ROS production via inhibition of Bax translocation (Park et al, 2012). Consistently, IGF1 increases m in HD striatal cells in a PI3K/AKT-dependent manner (Ribeiro et al, 2014).…”

Section: The Effects Of Gh-ghr-igf1 Axis On Mitochondrial Functionmentioning

confidence: 84%

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

Zhang

2021

Front. Cell Dev. Biol.

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Mitochondrial function is multifaceted in response to cellular energy homeostasis and metabolism, with the generation of adenosine triphosphate (ATP) through the oxidative phosphorylation (OXPHOS) being one of their main functions. Selective elimination of mitochondria by mitophagy, in conjunction with mitochondrial biogenesis, regulates mitochondrial function that is required to meet metabolic demand or stress response. Growth hormone (GH) binds to the GH receptor (GHR) and induces the JAK2/STAT5 pathway to activate the synthesis of insulin-like growth factor 1 (IGF1). The GH–GHR–IGF1 axis has been recognized to play significant roles in somatic growth, including cell proliferation, differentiation, division, and survival. In this review, we describe recent discoveries providing evidence for the contribution of the GH–GHR–IGF1 axis on mitochondrial biogenesis, mitophagy (or autophagy), and mitochondrial function under multiple physiological conditions. This may further improve our understanding of the effects of the GH–GHR–IGF1 axis on mitochondrial function, which may be controlled by the delicate balance between mitochondrial biogenesis and mitophagy. Specifically, we also highlight the challenges that remain in this field.

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“…MiR‐365 was shown to target Bcl‐2, and a positive correlation between IGF‐1 and Bcl‐2 in airway epithelial cells was reported. In contrast, IGF‐1 can block Bax translocation, with an anti‐oxidative effect in neuronal cells. Hamada et al .…”

Section: Discussionmentioning

confidence: 99%

Pro‐apoptotic effects of micro‐ribonucleic acid‐365 on retinal neurons by targeting insulin‐like growth factor‐1 in diabetic rats: An in vivo and in vitro study

Zheng

Wang

Shen

et al. 2018

J of Diabetes Invest

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Aims/ObjectiveThe present study aimed to explore the effects of micro‐ribonucleic acid‐365 (miR‐365) on apoptosis of retinal neurons by targeting insulin‐like growth factor‐1 (IGF‐1) in diabetes mellitus rats.Materials and MethodsHigh glucose‐induced retinal neurons were assigned into the blank (with no plasmid transfection), negative control (with plasmid transfection), anti‐miR‐365 (transfected miR‐365 antagomir), transfected IGF‐1 short hairpin RNA plasmid (sh‐IGF‐1) and transfected miR‐365 antagomir and IGF‐1 shRNA plasmid (anti‐miR‐365 + sh‐IGF‐1) groups. Proliferation and apoptosis of retinal neurons were detected by 5‐ethynyl‐2′‐deoxyuridine assay and Hoechst 33342 staining, respectively. Expressions of miR‐365, IGF‐1, Bcl‐2‐associated X protein (Bax) and Bcl‐2 were determined by reverse transcription quantitative polymerase chain reaction and western blotting. A control group contained 10 healthy rats. Terminal deoxynucleotidyl transferase dUTP nick‐end labeling staining was used to evaluate apoptosis of retinal neurons in rats.ResultsIn the anti‐miR‐365 group, the apoptosis rate and Bax expression were reduced in comparison with the negative control and blank groups, whereas the sh‐IGF‐1 and anti‐miR‐365 + sh‐IGF‐1 groups presented an opposite trend. Compared with the normal group, expressions of miR‐365 and Bax were increased, and expressions of IGF‐1 and Bcl‐2 were decreased, with more apoptotic cells in diabetes mellitus rat models. The sh‐IGF‐1 group had lower Bax expression, and higher expressions of IGF‐1 and Bcl‐2 with fewer apoptotic cells. Additionally, Bax expression was upregulated, expressions of IGF‐1 and Bcl‐2 were downregulated, and apoptotic cells were higher in the anti‐miR‐365 + sh‐IGF‐1 groups than the anti‐miR‐365 group.ConclusionThe results of the present study suggest that suppressed miR‐365 increases the IGF‐1 expression, leading to anti‐apoptotic effects on retinal neurons in diabetic rats.

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Insulin-like growth factor-1 protects against prion peptide-induced cell death in neuronal cells via inhibition of Bax translocation

Cited by 15 publications

References 31 publications

IGF-1 protects SH-SY5Y cells against MPP+-induced apoptosis via PI3K/PDK-1/Akt pathway

IGF-1 protects SH-SY5Y cells against MPP+-induced apoptosis via PI3K/PDK-1/Akt pathway

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

Pro‐apoptotic effects of micro‐ribonucleic acid‐365 on retinal neurons by targeting insulin‐like growth factor‐1 in diabetic rats: An in vivo and in vitro study

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