The Role of Gap Junction-Mediated Endothelial Cell–Cell Interaction in the Crosstalk between Inflammation and Blood Coagulation

Okamoto, Takayuki; Suzuki, Koji

doi:10.3390/ijms18112254

Cited by 53 publications

(40 citation statements)

References 121 publications

(165 reference statements)

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“…GJIC is essential for the maintenance of tissue and organ homeostasis and function (Contreras et al, ; Okamoto & Suzuki, ). In particular, GJIC plays an indispensable role in spermatogenesis in the testis, namely by building direct communication points between Sertoli cells (Roscoe, Barr, Mhawi, Pomerantz, & Kidder, ).…”

Section: Discussionmentioning

confidence: 99%

Benzo[a]pyrene‐decreased gap junctional intercellular communication via calcium/calmodulin signaling increases apoptosis in TM4 cells

Chou

et al. 2018

J of Applied Toxicology

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The mechanism of male reproductive toxicity induced by benzo[a]pyrene (BaP) is poorly understood. Gap junctional intercellular communication (GJIC) is known to play a critical role in maintaining spermatogenesis. The aim of the present study was to determine the toxic effects of BaP in Sertoli cells, and to explore the possibility and potential mechanisms of BaP-induced changes in the level of GJIC, and the relationship between GJIC and BaP-induced apoptosis. We treated mouse Sertoli cell lines (TM4) with different concentrations (0.1-100 μm) of BaP for 1-48 hours, and found that GJIC exhibited a dose- and time-dependent downregulation. Treatment with 10 μm BaP increased apoptosis, intracellular Ca level ([Ca ] ) and calmodulin (CaM) protein expression, and decreased the protein level of connexin 43 (Cx43) (also known as gap junction α-1 protein [GJA1]) in TM4 cells. However, BaP had no effect on the phosphorylation of Cx43 at Ser279/282, Ser255, Ser368 or Ser262. Downregulation of [Ca ] by BAPTA-AM significantly attenuated the BaP-induced GJIC suppression, Cx43 protein decrease and CaM protein increase. Interestingly, inhibition of CaM expression by W7 partially recovered BaP-induced GJIC inhibition, but had no effect on BaP-induced Cx43 protein decrease. Pretreatment with the GJIC activator retinoic acid significantly mitigated BaP-induced apoptosis. In conclusion, these results suggest that BaP can decrease GJIC via Ca /CaM signaling, and that BaP-induced GJIC suppression increases apoptosis in TM4 cells.

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Section: Discussionmentioning

confidence: 99%

Benzo[a]pyrene‐decreased gap junctional intercellular communication via calcium/calmodulin signaling increases apoptosis in TM4 cells

Chou

et al. 2018

J of Applied Toxicology

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“…Blood endothelial cell (BEC) junctions include adherens junctions expressing VE-cadherin, tight junctions expressing claudins and gap junctions characterized by connexin expression. BEC junctions are involved in a range of blood vascular processes, such as vasculogenesis, angiogenesis, vessel leak and leukocyte extravasation (Dejana et al, 2009b;Muller, 2015;Okamoto and Suzuki, 2017;Szymborska and Gerhardt, 2018). LEC junctions, on the other hand, have unique structural characteristics reflecting the specific demands of the lymphatic vasculature.…”

Section: Introductionmentioning

confidence: 99%

Lymphatic Endothelial Cell Junctions: Molecular Regulation in Physiology and Diseases

Zhang

Zarkada

et al. 2020

Front. Physiol.

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Lymphatic endothelial cells (LECs) lining lymphatic vessels develop specialized cell-cell junctions that are crucial for the maintenance of vessel integrity and proper lymphatic vascular functions. Successful lymphatic drainage requires a division of labor between lymphatic capillaries that take up lymph via open "button-like" junctions, and collectors that transport lymph to veins, which have tight "zipper-like" junctions that prevent lymph leakage. In recent years, progress has been made in the understanding of these specialized junctions, as a result of the application of state-of-the-art imaging tools and novel transgenic animal models. In this review, we discuss lymphatic development and mechanisms governing junction remodeling between button and zipper-like states in LECs. Understanding lymphatic junction remodeling is important in order to unravel lymphatic drainage regulation in obesity and inflammatory diseases and may pave the way towards future novel therapeutic interventions.

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“…The astrocytes are excitable but do not express action potentials. They are equipped with Ca 2+ signaling systems, which can be inter- and/or extracellular, and transport of small molecules between the cells occurs through gap junctions [ 4 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effects induced by pharmaceutical substances on inflammatory active brain astrocytes—promising treatment of neuroinflammation

Hanssoń

Björklund

Skiöldebrand

et al. 2018

J Neuroinflammation

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BackgroundPharmaceutical treatment with probable anti-inflammatory substances that attack cells in various ways including receptors, ion channels, or transporter systems may slow down the progression of inflammatory conditions. Astrocytes and microglia are the most prominent target cells for inflammation in the central nervous system. Their responses upon inflammatory stimuli work through the NO/cyclic GMP/protein kinase G systems that can downregulate the ATP-induced Ca2+ signaling, as well as G protein activities which alter Na+ transporters including Na+/K+-ATPase pump activity, Toll-like receptor 4 (TLR4), glutamate-induced Ca2+ signaling, and release of pro-inflammatory cytokines. The rationale for this project was to investigate a combination of pharmaceutical substances influencing the NO and the Gi/Gs activations of inflammatory reactive cells in order to make the cells return into a more physiological state. The ATP-evoked Ca2+ signaling is important maybe due to increased ATP release and subsequent activation of purinergic receptors. A balance between intercellular Ca2+ signaling through gap junctions and extracellular signaling mediated by extracellular ATP may be important for physiological function.MethodsAstrocytes in primary cultures were incubated with lipopolysaccharide in a physiological glucose concentration for 24 h to induce inflammatory reactivity. The probable anti-inflammatory substances sildenafil and 1α,25-Dihydroxyvitamin D3 together with endomorphin-1, naloxone, and levetiracetam, were used in the presence of high glucose concentration in the medium to restore the cells. Glutamate-, 5-HT-, and ATP-evoked intracellular Ca2+ release, Na+/K+-ATPase expression, expression of inflammatory receptors, and release of tumor necrosis factor alpha were measured.ResultsSildenafil in ultralow concentration together with 1α,25-Dihydroxyvitamin D3 showed most prominent effects on the ATP-evoked intracellular Ca2+ release. The μ-opioid agonist endomorphin-1, the μ-opioid antagonist naloxone in ultralow concentration, and the antiepileptic agent levetiracetam downregulated the glutamate-evoked intracellular Ca2+ release and TLR4. The combination of the pharmaceutical substances in high glucose concentration downregulated the glutamate- and ATP-evoked Ca2+ signaling and the TLR4 expression and upregulated the Na+/K+-ATPase pump.ConclusionPharmaceutical treatment with the combination of substances that have potential anti-inflammatory effects, which attack different biochemical mechanisms in the cells may exert decisive effects to downregulate neuroinflammation in the nervous system.

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The Role of Gap Junction-Mediated Endothelial Cell–Cell Interaction in the Crosstalk between Inflammation and Blood Coagulation

Cited by 53 publications

References 121 publications

Benzo[a]pyrene‐decreased gap junctional intercellular communication via calcium/calmodulin signaling increases apoptosis in TM4 cells

Benzo[a]pyrene‐decreased gap junctional intercellular communication via calcium/calmodulin signaling increases apoptosis in TM4 cells

Lymphatic Endothelial Cell Junctions: Molecular Regulation in Physiology and Diseases

Anti-inflammatory effects induced by pharmaceutical substances on inflammatory active brain astrocytes—promising treatment of neuroinflammation

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