The PPARγ agonist Troglitazone induces autophagy, apoptosis and necroptosis in bladder cancer cells

Yan, Siyuan; Yang, Xin; Chen, T; Xi, Zhijun; Jiang, Xuejun

doi:10.1038/cgt.2014.16

Cited by 50 publications

(46 citation statements)

References 38 publications

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“…However, the role of PPARγ-mediated transcriptional regulation of autophagy remains controversial. Indeed, Troglitazone, a PPARγ agonist, induces autophagy and cell death in bladder cancer cells (Yan et al, 2014), whereas another PPAR agonist, 15d-prostaglandin J 2 , suppresses autophagy in ischemic brain (Xu et al, 2013;Qin et al, 2015).…”

Section: Jun -Activated By Diverse Stressesmentioning

confidence: 99%

Transcriptional regulation of mammalian autophagy at a glance

Füllgrabe

Ghislat

Cho

et al. 2016

Journal of Cell Science

171

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Macroautophagy, hereafter referred to as autophagy, is a catabolic process that results in the lysosomal degradation of cytoplasmic contents ranging from abnormal proteins to damaged cell organelles. It is activated under diverse conditions, including nutrient deprivation and hypoxia. During autophagy, members of the core autophagy-related (ATG) family of proteins mediate membrane rearrangements, which lead to the engulfment and degradation of cytoplasmic cargo. Recently, the nuclear regulation of autophagy, especially by transcription factors and histone modifiers, has gained increased attention. These factors are not only involved in rapid responses to autophagic stimuli, but also regulate the long-term outcome of autophagy. Now there are more than 20 transcription factors that have been shown to be linked to the autophagic process. However, their interplay and timing appear enigmatic as several have been individually shown to act as major regulators of autophagy. This Cell Science at a Glance article and the accompanying poster highlights the main cellular regulators of transcription involved in mammalian autophagy and their target genes.

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Section: Jun -Activated By Diverse Stressesmentioning

confidence: 99%

Transcriptional regulation of mammalian autophagy at a glance

Füllgrabe

Ghislat

Cho

et al. 2016

Journal of Cell Science

171

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“…A previous study indicated that the PPARγ agonist troglitazone induces autophagy, apoptosis and necroptosis in bladder cancer cells [27]. However, rosiglitazone, a selective PPAR-γ-inhibitor, is reported to induce autophagy in H295R cells and cell cycle deregulation in SW13 adrenocortical cancer cells [28].…”

Section: Discussionmentioning

confidence: 99%

TRPML1 Participates in the Progression of Alzheimer’s Disease by Regulating the PPARγ/AMPK/Mtor Signalling Pathway

Zhang

Fang

Chen

et al. 2017

Cell Physiol Biochem

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Background: TRPML1 is reported to be involved in the pathogenesis of Alzheimer’s disease (AD) by regulating autophagy; however, the underlying mechanism is not completely clear. Methods: We developed an APP/PS1 transgenic animal model that presents with AD. TRPML1 was also overexpressed in these mice. Protein expression levels were determined by Western blot. Morris water maze (MWM) and recognition tasks were performed to characterize cognitive ability. TUNEL assays were analysed for the detection of neuronal apoptosis. Primary neurons were isolated and treated with the vehicle, Aβ1-42 or Aβ1-42 + mTOR activator, as well as infected with the recombinant adenovirus TRPML1 overexpression vector in vitro. Cell viability was measured by the MTS assay, and lysosomal Ca²⁺ was also measured. Results: In the APP/PS1 transgenic mice, TRPML1 was downregulated, the PPARγ/AMPK signalling pathway was activated, the mTOR/S6K signalling pathway was suppressed, and autophagic lysosome reformation (ALR)-related proteins were upregulated. TRPML1 overexpression or treatment with PPARγ and AMPK inhibitors or an mTOR activator reduced the expression levels of ALR-related proteins, rescued the memory and recognition impairments and attenuated neuronal apoptosis in mice with the APP/PS1 transgenes. In vitro experiments showed that TRPML1 overexpression or treatment with the mTOR activator propranolol attenuated the Aβ1-42-suppressed cell viability and the Aβ1-42-decreased lysosomal [Ca²⁺] ion concentration in primary neurons. TRPML1 overexpression or treatment with the mTOR activator propranolol also attenuated the Aβ1-42-inhibited mTOR/S6K signalling pathway and the Aβ1-42-induced ALR-related protein expression levels. Conclusion: TRPML1 is involved in the pathogenesis of AD by regulating autophagy at least in part through the PPARγ/AMPK/mTOR signallingpathway.

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“…PPAR gamma is also present in other tissues, such as breast [70,71], colon [72][73][74], lung [75,76], ovary [77,78], prostate [79,80] and thyroid [81,82] wherein it mediates several specific functions, such as early development [83], cell proliferation [84], differentiation [85], apoptosis [86], and metabolic homeostasis [87]. Many investigators [88][89][90][91][92][93][94][95][96][97] reported that PPAR gamma was also involved in the control of transcriptional regulation of autophagy. The target genes of PPAR gamma has been reported including ATG7, ATG12, LC3, P62, ULK1, LAMP1, BCL2, Beclin1, Pink1, and Bnip3 [88][89][90][91][92][93][94][95][96][97] (Table 1).…”

Section: Newly Participant Of Autophagy Regulation: Pparsmentioning

confidence: 99%