AMP-activated protein kinase inhibits MPP+-induced oxidative stress and apoptotic death of SH-SY5Y cells through sequential stimulation of Akt and autophagy

Jovanović-Tucović, Maja; Harhaji-Trajković, Ljubica; Dulović, Marija; Zogović, Nevena; Jeremic, Marija; Mandić, Miloš; Kostić, Vladimir; Trajkovič, Vladimir; Marković, Ivanka

doi:10.1016/j.ejphar.2019.172677

Cited by 20 publications

(20 citation statements)

References 72 publications

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“…Recent research has revealed that the process of mammary gland involution during the early years is accomplished by both apoptosis and autophagy [19,20]. In addition to the regulation of endocrine hormones, local cytokines also become the focus of research on the autophagy and apoptosis during mammary gland involution.…”

Section: Discussionmentioning

confidence: 99%

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Induction of Chemerin on Autophagy and Apoptosis in Dairy Cow Mammary Epithelial Cells

Song

Tang

et al. 2019

Animals

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Simple SummaryThe process of mammary gland involution during the early is accomplished by both apoptosis and autophagy. Chemerin, a novel adipocytokine, plays a pivotal role in immune response and lipid metabolism, which was involved in the regulation of programmed cell death. This study focused on the relationship between autophagy and apoptosis in the presence of Chemerin in bovine mammary epithelial cells (BMECs). The results indicated that Chemerin could activate the complete autophagy process and induce apoptotic cascade in BMECs. The addition of Chloroquine (CQ), an inhibitor of autophagy, prompted Chemerin to have more obvious effects on apoptosis-related factors, which suggests that Chemerin-induced autophagy involves the intrinsic apoptotic pathway of BMECs. We found that the pro-apoptotic potential of Chemerin is further enhanced under conditions in which autophagy is effectively inhibited. Thus, exploring the role of autophagy and apoptosis on the involution of mammary epithelial cells will undoubtedly be of great importance in productivity improvement of dairy animals. AbstractInvolution of the mammary gland is a complex process controlled by various endocrine hormones and cytokine. As a novel adipocytokine, Chemerin not only plays a pivotal role in physiological and pathological processes such as immune response and lipid metabolism, but is also involved in the regulation of programmed cell death, including autophagy and apoptosis. The purpose of the present study was to elucidate whether autophagy and apoptosis of bovine mammary epithelial cells (BMECs) was triggered by Chemerin. BMECs were cultured and treated with Chemerin in vitro. The expression of autophagosome-forming marker, microtubule-associated protein 1 light chain 3 II (LC3-II) and sequestosome-1 (SQSTM 1, best known as p62), a substrate of autophagosome degradation were detected. The result showed that Chemerin significantly decreased the expression of p62 and markedly induced the conversion of LC3-I to LC3-II. The ratio of Bcl2-associated X and B-cell lymphoma-2 (Bax/Bcl-2) and the activity of caspase-3 were up-regulated after being treated by Chemerin, and the apoptotic rate was also significantly increased. These results suggested that Chemerin promoted the occurrence of autophagy and apoptosis in BMECs. Chloroquine (CQ), which is an inhibitor of autophagy. To explore effects of Chemerin on apoptosis, we prevented Chemerin-induced autophagy by pre-adding CQ in BMECs. Interestingly, this part of the experiment helped us find that all effects of Chemerin on apoptosis of BMECs could be enhanced with the inhibition of autophagy. Our study demonstrates that Chemerin-induced autophagy and apoptosis are mutually regulated in BMECs, but the specific mechanism remains to be further researched.

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Section: Discussionmentioning

confidence: 99%

“…The mammary gland forms apoptotic bodies by DNA fragmentation and chromatin condensation to reduce the number of bovine mammary epithelial cells after weaning [19]. Cell apoptosis is an initiative cell death under a series of genes regulation.…”

Section: Discussionmentioning

confidence: 99%

Induction of Chemerin on Autophagy and Apoptosis in Dairy Cow Mammary Epithelial Cells

Song

Tang

et al. 2019

Animals

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“…The regulatory effects of MPTP/MPP + on autophagy are not consistent among different studies. MPTP/MPP + treatment increases autophagosome formation, increases p62 levels, and decreases lysosomal activity ( Dehay et al, 2010 ; Lim et al, 2011 ; Lim et al, 2014 ; Jovanovic-Tucovic et al, 2019 ), indicating that autophagy initiation is activated but autophagic flux is blocked by MPP + treatment. The activation of autophagy initiation by MPP + treatment probably occurs through activation of AMPK ( Jovanovic-Tucovic et al, 2019 ).…”

Section: Er Stress Upr and Autophagy Cross Talk In Pd Pathogenesismentioning

confidence: 99%

“…MPTP/MPP + treatment increases autophagosome formation, increases p62 levels, and decreases lysosomal activity ( Dehay et al, 2010 ; Lim et al, 2011 ; Lim et al, 2014 ; Jovanovic-Tucovic et al, 2019 ), indicating that autophagy initiation is activated but autophagic flux is blocked by MPP + treatment. The activation of autophagy initiation by MPP + treatment probably occurs through activation of AMPK ( Jovanovic-Tucovic et al, 2019 ). Further study indicates that mild MPP + exposure (10 or 200 μM for 48 h) predominantly inhibits autophagic degradation by reducing lysosomal hydrolase cathepsin D activity, whereas acute MPP + treatment (2.5 and 5 mM for 24 h) inhibits both autophagic degradation and basal autophagy by decreasing lysosomal density ( Miyara et al, 2016 ).…”

Section: Er Stress Upr and Autophagy Cross Talk In Pd Pathogenesismentioning

confidence: 99%

“…MPP + treatment-induced ER stress and the UPR closely contribute to autophagy induction and autophagic flux blockage. All branches of the UPR are activated by MPTP/MPP + treatment, as well as subsequent events such as activation of AMPK ( Jovanovic-Tucovic et al, 2019 ), decreased mTOR activity ( Selvaraj et al, 2012 ), and increased NF-κB signaling ( Ghribi et al, 2003 ), which contribute to autophagy initiation ( Zhu et al, 2017 ). MPTP/MPP + treatment also disrupts lysosomal functions and leads to autophagic flux blockage ( Dehay et al, 2010 ; Lim et al, 2011 ).…”

Section: Er Stress Upr and Autophagy Cross Talk In Pd Pathogenesismentioning

confidence: 99%

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The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson’s Disease

Ren

Zhai

et al. 2021

Front. Aging Neurosci.

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Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, and it is characterized by the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), as well as the presence of intracellular inclusions with α-synuclein as the main component in surviving DA neurons. Emerging evidence suggests that the imbalance of proteostasis is a key pathogenic factor for PD. Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and autophagy, two major pathways for maintaining proteostasis, play important roles in PD pathology and are considered as attractive therapeutic targets for PD treatment. However, although ER stress/UPR and autophagy appear to be independent cellular processes, they are closely related to each other. In this review, we focused on the roles and molecular cross-links between ER stress/UPR and autophagy in PD pathology. We systematically reviewed and summarized the most recent advances in regulation of ER stress/UPR and autophagy, and their cross-linking mechanisms. We also reviewed and discussed the mechanisms of the coexisting ER stress/UPR activation and dysregulated autophagy in the lesion regions of PD patients, and the underlying roles and molecular crosslinks between ER stress/UPR activation and the dysregulated autophagy in DA neurodegeneration induced by PD-associated genetic factors and PD-related neurotoxins. Finally, we indicate that the combined regulation of ER stress/UPR and autophagy would be a more effective treatment for PD rather than regulating one of these conditions alone.

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No energy, no autophagy—Mechanisms and therapeutic implications of autophagic response energy requirements

Mandic,

Paunovic,

Vucicevic

et al. 2024

Journal Cellular Physiology

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Autophagy is a lysosome‐mediated self‐degradation process of central importance for cellular quality control. It also provides macromolecule building blocks and substrates for energy metabolism during nutrient or energy deficiency, which are the main stimuli for autophagy induction. However, like most biological processes, autophagy itself requires ATP, and there is an energy threshold for its initiation and execution. We here present the first comprehensive review of this often‐overlooked aspect of autophagy research. The studies in which ATP deficiency suppressed autophagy in vitro and in vivo were classified according to the energy pathway involved (oxidative phosphorylation or glycolysis). A mechanistic insight was provided by pinpointing the critical ATP‐consuming autophagic events, including transcription/translation/interaction of autophagy‐related molecules, autophagosome formation/elongation, autophagosome fusion with the lysosome, and lysosome acidification. The significance of energy‐dependent fine‐tuning of autophagic response for preserving the cell homeostasis, and potential implications for the therapy of cancer, autoimmunity, metabolic disorders, and neurodegeneration are discussed.

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AMP-activated protein kinase inhibits MPP+-induced oxidative stress and apoptotic death of SH-SY5Y cells through sequential stimulation of Akt and autophagy

Cited by 20 publications

References 72 publications

Induction of Chemerin on Autophagy and Apoptosis in Dairy Cow Mammary Epithelial Cells

Induction of Chemerin on Autophagy and Apoptosis in Dairy Cow Mammary Epithelial Cells

The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson’s Disease

No energy, no autophagy—Mechanisms and therapeutic implications of autophagic response energy requirements

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