p38 MAPK activation coupled to endocytosis is a determinant of endothelial monolayer integrity

Siddiqui, Shahid; Siddiqui, Zeba K.; Uddin, Shahab; Minshall, Richard D.; Malik, Asrar B.

doi:10.1152/ajplung.00257.2005

Cited by 18 publications

(15 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, caveolin-1 was proved to interact with p38 and facilitate its phosphorylation in rat lung microvessel endothelial cells, which contributed to maintain endothelial monolayer integrity. 50 In vascular endothelial cells, the PCB77-induced upregulation of monocyte chemoattractant protein-1 was demonstrated to be dependent on caveolin-1 and could also be prevented by inhibiting p38 activity. 51 In our study, the signaling mechanism that associates Aroclor1254 to the increment of caveolin-1 was verified to be the elevated p38 activity and could be antagonized by SB203580.…”

Section: Discussionmentioning

confidence: 99%

Aroclor1254 disrupts the blood–testis barrier by promoting endocytosis and degradation of junction proteins via p38 MAPK pathway

Jia

et al. 2017

Cell Death Dis

View full text Add to dashboard Cite

The blood–testis barrier (BTB) constituted by coexisting junction apparatus between Sertoli cells (SCs) plays an important role in spermatogenesis, which is a known target of various environmental toxicants. The commercial polychlorinated biphenyls mixture, Aroclor1254, has been shown to impair male reproduction by decreasing sperm count and affecting SC metabolism. This study was designed to investigate the effects of Aroclor1254 on the BTB integrity and elucidate the underlying mechanisms. We found that Aroclor1254 treatment in rats (1 or 3 mg/kg per day for 21 consecutive days) and in primary cultured SCs (5 or 10 μg/ml for 48 h) could induce BTB disruption via p38 MAPK pathway, concurrently with increments in junction proteins (JAM-A, N-cadherin, and β-catenin) endocytosis, and occludin ubiquitination. Either inhibition of caveolin-dependent membrane protein internalization by cholesterol oxidase or silencing E3 ubiquitine ligase Itch by small interfering RNA could partially counteract the effects of Aroclor1254 on the barrier function of cultured SCs. These results demonstrate that Aroclor1254 disrupts the BTB function by promoting the caveolin-dependent endocytosis and ubiquitine–proteasome degradation of junction proteins through the p38 MAPK pathway, which might be the potential reasons for its negative effects on spermatogenesis and male reproduction.

show abstract

Section: Discussionmentioning

confidence: 99%

Aroclor1254 disrupts the blood–testis barrier by promoting endocytosis and degradation of junction proteins via p38 MAPK pathway

Jia

et al. 2017

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…Their collective experience in these cav-1 knock out mice clearly demonstrated a lack of caveolae biogenesis and an association with greatly depressed accumulation of albumin. The compensatory hyperpermeability to albumin in cav-1 null mice has been ascribed to increased NO biosynthesis and the molecular details accounting for increased paracellular transport in the absence of transcytosis have been delineated in vivo [24,25,35] and in cell culture [21]. As such, pulmonary endothelium has been a useful prototype to advance fundamental aspects of cell biology and contribute to the ongoing debate [36] of relative contributions of transcytosis [9,37] and paracellular [38] pathways or both [39] to determinants of vascular permeability.…”

Section: Discussionmentioning

confidence: 99%

Caveolae-Dependent and -Independent Uptake of Albumin in Cultured Rodent Pulmonary Endothelial Cells

Wasserloos

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

Although a critical role for caveolae-mediated albumin transcytosis in pulmonary endothelium is well established, considerably less is known about caveolae-independent pathways. In this current study, we confirmed that cultured rat pulmonary microvascular (RPMEC) and pulmonary artery (RPAEC) endothelium endocytosed Alexa488-labeled albumin in a saturable, temperature-sensitive mode and internalization resulted in co-localization by fluorescence microscopy with cholera B toxin and caveolin-1. Although siRNA to caveolin-1 (cav-1) in RPAEC significantly inhibited albumin uptake, a remnant portion of albumin uptake was cav-1-independent, suggesting alternative pathways for albumin uptake. Thus, we isolated and cultured mouse lung endothelial cells (MLEC) from wild type and cav-1-/- mice and noted that ~ 65% of albumin uptake, as determined by confocal imaging or live cell total internal reflectance fluorescence microscopy (TIRF), persisted in total absence of cav-1. Uptake of colloidal gold labeled albumin was evaluated by electron microscopy and demonstrated that albumin uptake in MLEC from cav-1-/- mice was through caveolae-independent pathway(s) including clathrin-coated pits that resulted in endosomal accumulation of albumin. Finally, we noted that albumin uptake in RPMEC was in part sensitive to pharmacological agents (amiloride [sodium transport inhibitor], Gö6976 [protein kinase C inhibitor], and cytochalasin D [inhibitor of actin polymerization]) consistent with a macropinocytosis-like process. The amiloride sensitivity accounting for macropinocytosis also exists in albumin uptake by both wild type and cav-1-/- MLEC. We conclude from these studies that in addition to the well described caveolar-dependent pulmonary endothelial cell endocytosis of albumin, a portion of overall uptake in pulmonary endothelial cells is cav-1 insensitive and appears to involve clathrin-mediated endocytosis and macropinocytosis-like process.

show abstract

“…In a related study we also found that caveolin-1 was required for ICAM-1 up-regulation by B[a]P in endothelial cells and that this effect was also mediated by p38 activation (Oesterling et al , 2008). In addition, caveolin-1 was demonstrated to bind p38 in endothelial cells and to facilitate its phosphorylation and activation of downstream targets (Siddiqui et al , 2007). These data all suggest that regulation of inflammatory pathways through caveolae might be a mechanism shared by environmental toxicants that are AhR agonists.…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of endothelial monocyte chemoattractant protein-1 by coplanar PCB77 is caveolin-1-dependent

Majkova

Smart

Toborek

et al. 2009

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Atherosclerosis, the primary cause of heart disease and stroke is initiated in the vascular endothelium, and risk factors for its development include environmental exposure to persistent organic pollutants. Caveolae are membrane microdomains involved in regulation of many signaling pathways, and in particular in endothelial cells. We tested the hypothesis that intact caveolae are required for coplanar PCB77-induced up-regulation of monocyte chemoattractant protein-1 (MCP-1), an endotheliumderived chemokine that attracts monocytes into sub-endothelial space in early stages of the atherosclerosis development. Atherosclerosis-prone LDL-R −/− mice (control) or caveolin-1 −/− /-LDL-R −/− mice were treated with PCB77. PCB77 induced aortic mRNA expression and plasma protein levels of MCP-1 in control, but not caveolin-1 −/− /LDL-R −/− mice. To study the mechanism of this effect, primary endothelial cells were used. PCB77 increased MCP-1 levels in endothelial cells in a time-and concentration-dependent manner. This effect was abolished by caveolin-1 silencing using siRNA. Also, MCP-1 up-regulation by PCB77 was prevented by inhibiting p38 and c-Jun N-terminal kinase (JNK), but not ERK1/2, suggesting regulatory functions via p38 and JNK MAPK pathways. Finally, pretreatment of endothelial cells with the aryl hydrocarbon receptor (AhR) inhibitor α-naphthoflavone (α-NF) partially blocked MCP-1 up-regulation. Thus, our data demonstrate that coplanar PCB77 can induce MCP-1 expression by endothelial cells and that this effect is mediated by AhR, as well as p 38 and JNK MAPK pathways. Intact caveolae are required for these processes both in vivo and in vitro. This further supports a key role for caveolae in vascular inflammation induced by persistent organic pollutants.

show abstract

p38 MAPK activation coupled to endocytosis is a determinant of endothelial monolayer integrity

Cited by 18 publications

References 30 publications

Aroclor1254 disrupts the blood–testis barrier by promoting endocytosis and degradation of junction proteins via p38 MAPK pathway

Aroclor1254 disrupts the blood–testis barrier by promoting endocytosis and degradation of junction proteins via p38 MAPK pathway

Caveolae-Dependent and -Independent Uptake of Albumin in Cultured Rodent Pulmonary Endothelial Cells

Up-regulation of endothelial monocyte chemoattractant protein-1 by coplanar PCB77 is caveolin-1-dependent

Contact Info

Product

Resources

About