Suppressive effect of AMP-activated protein kinase on the epithelial-mesenchymal transition in retinal pigment epithelial cells

Chen

Environmental Toxicology

et al. 2019

Prospective cohort studies have indicated that a highly nickel-polluted environment may severely affect human health, resulting in such conditions as respiratory tract cancers. Such exposure can trigger vascular endothelial growth factor (VEGF) expression. However, the signal transduction pathways leading to VEGF induction by nickel compounds are not well understood.This study revealed the occurrence of VEGF induction in human non-small-cell lung cancer H460 cells exposed to NiCl 2 . Moreover, exposing H460 cells to NiCl 2 activated extracellular signal-regulated protein kinase (ERK), nuclear factor kappa B (NFκB), and protein kinase B (Akt) as well as downregulated AMP activated protein kinase (AMPK) expression. The mitogen-activated

Section: Resultssupporting

confidence: 51%

Nickel‐induced VEGF expression via regulation of Akt, ERK1/2, NFκB, and AMPK pathways in H460 cells

Chen

Environmental Toxicology

et al. 2019

“…The activated SMADs combine with SMAD4 to form a SMAD complex, which then enters the nucleus and combines with regulatory elements to regulate the expression of key genes associated with EMT. In addition to SMAD-dependent signaling, TGF β induces EMT through SMAD independent signaling pathways including Rho GTPase-dependent pathways ( Lee, Ko & Joo, 2008 ), PI3K/Akt pathway ( Huang et al, 2017 ; Yokoyama et al, 2012 ), mitogen-activated kinase (MAPK) pathways ( Chen et al, 2017 ; Lee et al, 2020 ; Matoba et al, 2017 ; Schiff et al, 2019 ) and Jagged/Notch signaling pathway ( Zhang et al, 2017 ). The MAPK signaling pathways include extracellular signal-regulated kinase(ERK) MAPK pathway, p38 MAPK pathway, and JUN N-terminal kinase (JNK) pathway ( Parrales et al, 2013 ; Schiff et al, 2019 ; Xiao et al, 2014 ; Zhang et al, 2018a ).…”

Section: Survey Methodologymentioning

confidence: 99%

Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy

Zou

Shan

et al. 2020

PeerJ

Under physiological conditions, retinal pigment epithelium (RPE) is a cellular monolayer composed of mitotically quiescent cells. Tight junctions and adherens junctions maintain the polarity of RPE cells, and are required for cellular functions. In proliferative vitreoretinopathy (PVR), upon retinal tear, RPE cells lose cell-cell contact, undergo epithelial-mesenchymal transition (EMT), and ultimately transform into myofibroblasts, leading to the formation of fibrocellular membranes on both surfaces of the detached retina and on the posterior hyaloids, which causes tractional retinal detachment. In PVR, RPE cells are crucial contributors, and multiple signaling pathways, including the SMAD-dependent pathway, Rho pathway, MAPK pathways, Jagged/Notch pathway, and the Wnt/β-catenin pathway are activated. These pathways mediate the EMT of RPE cells, which play a key role in the pathogenesis of PVR. This review summarizes the current body of knowledge on the polarized phenotype of RPE, the role of cell-cell contact, and the molecular mechanisms underlying the RPE EMT in PVR, emphasizing key insights into potential approaches to prevent PVR.

“…How this broad reprogramming of membrane traffic by AMPK contributes to some of the established cell and tissue outcomes of AMPK is an important area of investigation with many open questions. For example, many studies have revealed that AMPK regulates epithelial‐mesenchymal transition (EMT), a cellular differentiation program that is important for development and tissue repair and that is also critical to progression of diseases such as cancer and kidney disease . Importantly, EMT elicits and requires broad remodeling of membrane traffic .…”

Section: Control Of Endocytic Membrane Traffic By Ampkmentioning

confidence: 99%

Energetic adaptations: Metabolic control of endocytic membrane traffic

Rahmani

Defferrari

Wakarchuk

et al. 2019

Traffic

Endocytic membrane traffic controls the access of myriad cell surface proteins to the extracellular milieu, and thus gates nutrient uptake, ion homeostasis, signaling, adhesion and migration. Coordination of the regulation of endocytic membrane traffic with a cell's metabolic needs represents an important facet of maintenance of homeostasis under variable conditions of nutrient availability and metabolic demand. Many studies have revealed intimate regulation of endocytic membrane traffic by metabolic cues, from the specific control of certain receptors or transporters, to broader adaptation or remodeling of the endocytic membrane network. We examine how metabolic sensors such as AMP‐activated protein kinase, mechanistic target of rapamycin complex 1 and hypoxia inducible factor 1 determine sufficiency of various metabolites, and in turn modulate cellular functions that includes control of endocytic membrane traffic. We also examine how certain metabolites can directly control endocytic traffic proteins, such as the regulation of specific protein glycosylation by limiting levels of uridine diphosphate N‐acetylglucosamine (UDP‐GlcNAc) produced by the hexosamine biosynthetic pathway. From these ideas emerge a growing appreciation that endocytic membrane traffic is orchestrated by many intrinsic signals derived from cell metabolism, allowing alignment of the functions of cell surface proteins with cellular metabolic requirements. Endocytic membrane traffic determines how cells interact with their environment, thus defining many aspects of nutrient uptake and energy consumption. We examine how intrinsic signals that reflect metabolic status of a cell regulate endocytic traffic of specific proteins, and, in some cases, exert broad control of endocytic membrane traffic phenomena. Hence, endocytic traffic is versatile and adaptable and can be modulated to meet the changing metabolic requirements of a cell.