Klotho-mediated changes in the expression of Atg13 alter formation of ULK1 complex and thus initiation of ER- and Golgi-stress response mediated autophagy

Mytych, Jennifer; Sołek, Przemysław; Będzińska, Agnieszka; Rusinek, Kinga; Warzybok, Aleksandra; Tabęcka-Łonczyńska, Anna; Koziorowski, Marek

doi:10.1007/s10495-019-01579-z

Cited by 11 publications

(5 citation statements)

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“…Then, sensors activate the following three downstream signaling pathways related to the Golgi response to stress: TFE3 (inducing Golgi expansion by regulating the transcriptional induction of Golgi-related genes), HSP47 (preventing Golgi stress-induced apoptosis), and CREB3 (inducing apoptosis through the transcriptional induction of ARF4) (Taniguchi and Yoshida, 2017). One previous study found that autophagy initiation allowed for the parallel activation of the TFE3 pathway (Mytych et al, 2020). Additionally, it has been proposed that core proteins accumulate in the Golgi, cause Golgi dysfunction, and induce autophagy of the Golgi apparatus.…”

Section: Effects Of Disrupted Formation Of Autophagy On Golgi Functionmentioning

confidence: 99%

“…Additionally, it has been proposed that core proteins accumulate in the Golgi, cause Golgi dysfunction, and induce autophagy of the Golgi apparatus. Subsequently, signal-inducing autophagy indirectly activates TFE3 (Taniguchi et al, 2015;Mytych et al, 2020). After activating TFE3, the Golgi expands in accordance with greater protein synthesis demands.…”

Section: Effects Of Disrupted Formation Of Autophagy On Golgi Functionmentioning

confidence: 99%

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Golgi Apparatus: A Potential Therapeutic Target for Autophagy-Associated Neurological Diseases

Deng

Liu

et al. 2020

Front. Cell Dev. Biol.

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Autophagy has dual effects in human diseases: appropriate autophagy may protect cells from stress, while excessive autophagy may cause cell death. Additionally, close interactions exist between autophagy and the Golgi. This review outlines recent advances regarding the role of the Golgi apparatus in autophagy. The signaling processes of autophagy are dependent on the normal function of the Golgi. Specifically, (i) autophagy-related protein 9 is mainly located in the Golgi and forms new autophagosomes in response to stressors; (ii) Golgi fragmentation is induced by Golgirelated proteins and accompanied with autophagy induction; and (iii) the endoplasmic reticulum-Golgi intermediate compartment and the reticular trans-Golgi network play essential roles in autophagosome formation to provide a template for lipidation of microtubule-associated protein 1A/1B-light chain 3 and induce further ubiquitination. Golgi-related proteins regulate formation of autophagosomes, and disrupted formation of autophagy can influence Golgi function. Notably, aberrant autophagy has been demonstrated to be implicated in neurological diseases. Thus, targeted therapies aimed at protecting the Golgi or regulating Golgi proteins might prevent or ameliorate autophagy-related neurological diseases. Further studies are needed to investigate the potential application of Golgi therapy in autophagy-based neurological diseases.

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Section: Effects Of Disrupted Formation Of Autophagy On Golgi Functionmentioning

confidence: 99%

Section: Effects Of Disrupted Formation Of Autophagy On Golgi Functionmentioning

confidence: 99%

Golgi Apparatus: A Potential Therapeutic Target for Autophagy-Associated Neurological Diseases

Deng

Liu

et al. 2020

Front. Cell Dev. Biol.

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“…siRNAs used were: Ctrl-siRNA (Silencer Negative Control No. 1 siRNA; #AM4611, Thermo Fisher Scientific) or KLTH-siRNA (UniGeneID Hs.524953; siRNA ID 15204; #AM16706, Thermo Fisher Scientific) [13][14][15]. Silencing of klotho was confirmed with the Western Blot method.…”

Section: Cell Culture Klth Silencing and Lps Treatmentmentioning

confidence: 99%

Focus on the Role of Klotho Protein in Neuro-Immune Interactions in HT-22 Cells Upon LPS Stimulation

Rusinek

Sołek

Tabęcka-Łonczyńska

et al. 2020

Cells

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Neuroinflammation is defined as the activation of the brain’s innate immune system in response to an inflammatory challenge and is considered to be a prominent feature of neurodegenerative diseases. The contribution of overactivated neuroglial cells to neuroinflammation and neurodegenerative disorders is well documented, however, the role of hippocampal neurons in the neuroinflammatory process remains fragmentary. In this study, we show for the first time, that klotho acts as a signal transducer between pro-survival and pro-apoptotic crosstalk mediated by ER stress in HT-22 hippocampal neuronal cells during LPS challenge. In control HT-22 cells, LPS treatment results in activation of the IRE1α-p38 MAPK pathway leading to increased secretion of anti-inflammatory IL-10, and thus, providing adaptation mechanism. On the other hand, in klotho-deficient HT-22 cells, LPS induces oxi-nitrosative stress and genomic instability associated with telomere dysfunctions leading to p53/p21-mediated cell cycle arrest and, in consequence, to ER stress, inflammation as well as of apoptotic cell death. Therefore, these results indicate that klotho serves as a part of the cellular defense mechanism engaged in the protection of neuronal cells against LPS-mediated neuroinflammation, emerging issues linked with neurodegenerative disorders.

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“…Autophagy can be measured by microtubule-associated proteins 1A/1B light chain 3B (LC3-II) protein expression levels. In the course of autophagy, the microtubuleassociated protein 1 light chain 3 (LC3-I) is transformed to LC3-II, which permits the combination of the protein to autophagosome membranes [17,[19][20][21]. So, light chain 3 (LC3) is a key autophagy proteins, which have a central role in the pathogenesis of DM vascular complications.…”

Section: Introductionmentioning

confidence: 99%

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2022

DOIJ

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Introduction:To study the protective efficacy of Empagliflozin (EMPA), a novel sodium glucose transporter inhibitor antidiabetic drug, on the expression of α-klotho (αKL) protein and of the autophagy key proteins Light chain 3 (LC3) in type 2 diabetic mellitus (T2DM) mice diabetic retinopathy (DR). Materials and Methods: We used the BTBR mouse strain with the ob/ob leptin-deficiency mutation that develops spontaneously severe T2DM, C57/BL mice used as control. EMPA was administrated to the diabetic mice via drinking water for a period of 12 weeks. At the end of the experiment, mice retinas were removed and subjected to further histological analysis: Immunohistochemistry and Immunofluorescence staining for αKL, LC3, protein expression level. Results: Retinal αKL protein expression levels were lower in diabetic mice than control (11.94±4.6 vs 48.4±5.33) % ** P< 0.01), which were restored to near normal with EMPA treatment compared to DM mice (35+20.4% vs 11.94±4.6%,*P<0.05). LC3 levels were increased in diabetic retinas compared to control (29.44±2.84 vs 15.6± 2.23) %, *** P<0.01, and increased with EMPA treatment compared to control (24.77±1.4% vs, 15.6±2.3% *P<0.05). There were no significant changes in ATG5 protein expression in the two groups of diabetic mice with or without EMPA. Conclusions: The data suggested that αKL protein and the autophagy proteins LC3 & ATG5 are involved in the pathogenesis of DR. Our data suggested that αKL and the autophagy key protein LC3 modulators could probably be potential protective factors against retinopathy develops in T2DM patients.

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Klotho-mediated changes in the expression of Atg13 alter formation of ULK1 complex and thus initiation of ER- and Golgi-stress response mediated autophagy

Cited by 11 publications

References 34 publications

Golgi Apparatus: A Potential Therapeutic Target for Autophagy-Associated Neurological Diseases

Golgi Apparatus: A Potential Therapeutic Target for Autophagy-Associated Neurological Diseases

Focus on the Role of Klotho Protein in Neuro-Immune Interactions in HT-22 Cells Upon LPS Stimulation

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