New Diseases Derived or Associated with the Tight Junction

Cereijido, Marcelino; Contreras, Rubén G.; Flores-Benítez, David; Flores-Maldonado, Catalina; Larre, Isabel; Ruiz, Agustı́n; Shoshani, Liora

doi:10.1016/j.arcmed.2007.02.003

Cited by 83 publications

(63 citation statements)

References 121 publications

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“…The ionic permeability of the TJ has been correlated with claudin expression (42). Similarly, the expression of different claudin isoforms has been shown to affect TER in MDCK cells (43).…”

Section: Discussionmentioning

confidence: 98%

Ouabain modulates epithelial cell tight junction

Larre

Lázaro

Contreras

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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102

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Epithelial cells treated with high concentrations of ouabain (e.g., 1 μM) retrieve molecules involved in cell contacts from the plasma membrane and detach from one another and their substrates. On the basis of this observation, we suggested that ouabain might also modulate cell contacts at low, nontoxic levels (10 or 50 nM). To test this possibility, we analyzed its effect on a particular type of cell-cell contact: the tight junction (TJ). We demonstrate that at concentrations that neither inhibit K + pumping nor disturb the K + balance of the cell, ouabain modulates the degree of sealing of the TJ as measured by transepithelial electrical resistance (TER) and the flux of neutral 3 kDa dextran (J DEX ). This modulation is accompanied by changes in the levels and distribution patterns of claudins 1, 2, and 4. Interestingly, changes in TER, J DEX , and claudins behavior are mediated through signal pathways containing ERK1/2 and c-Src, which have distinct effects on each physiological parameter and claudin type. These observations support the theory that at low concentrations, ouabain acts as a modulator of cell-cell contacts.claudins | c-Src | ERK1/2 | Madin-Darby canine kidney | occludin S everal lines of evidence, including the high affinity and specificity of ouabain for Na + ,K + -ATPase, suggest that endogenous ouabain analogs might exist. In keeping with this possibility, Hamlyn et al.(1) demonstrated the presence of a substance in plasma that cannot be distinguished from ouabain even by specific antibodies and mass spectrometry (1-4). Endogenous ouabain levels are increased during exercise (5) and in pathological conditions such as arterial hypertension (6-9) and eclampsia (10), raising the possibility that ouabain functions as a hormone and prompting efforts to elucidate physiological role.We have previously demonstrated that ouabain acts on cell-substrate and cell-cell contacts in Madin-Darby canine kidney (MDCK) cells. At 1 μM, ouabain binding to the Na + ,K + -ATPase results in pump inhibition and disassembly of molecules from the tight, adherens, and focal junctions (i.e., a P→A mechanism from pump to adhesion) (11). Consistent with these results, Rajasekaran et al. (12) have observed that 0.5 μM ouabain acts on the tight junction (TJ), decreasing transepithelial electrical resistance (TER) and increasing mannitol and inulin permeability in cultures of human retinal pigment epithelial cells. Furthermore, we have shown that in cocultures of wild-type MDCK and ouabain-resistant MDCK cells, ouabain treatment increases the expression of connexin 32, but not 26 or 43, and increases cell-cell communication via gap junctions to rescue the wild-type cells (13). Although these effects indicate that toxic levels of ouabain affect the structure and function of cell-cell junctions, we do not know how lower levels of ouabain affect adhesive structures.In the present work, we focus on this question and demonstrate that 10 nM ouabain affects neither Na + ,K + -ATPase nor the K + balance of the cells and does not indu...

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“…The ionic permeability of the TJ has been correlated with claudin expression (42). Similarly, the expression of different claudin isoforms has been shown to affect TER in MDCK cells (43).…”

Section: Discussionmentioning

confidence: 98%

Ouabain modulates epithelial cell tight junction

Larre

Lázaro

Contreras

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

102

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“…Consequently infants are susceptible to conditions such as infectious diarrhoea, necrotising enterocolitis and allergic gastroenteropathy (Schreiber & Walker, 1988). It is essential that the infant intestinal barrier matures appropriately because barrier dysfunction in adulthood is a critical factor in predisposition to intestinal diseases (Groschwitz & Hogan, 2009) and is associated with autoimmune diseases in other parts of the body (Cereijido et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The Role of Intestinal Barrier Function in Early Life in the Development of Colitis

Anderson¹,

Dalziel²,

Gopal³

et al. 2012

Colitis

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“…The primary seal of the TJs is a complex interaction of numerous transmembrane, accessory, and cytoskeletal proteins-the transmembrane proteins occludin and the claudins, with the accessory protein zonula occludens-1 (ZO-1) interacting with their C termini, are linked to the actin cytoskeleton (Farshori and Kachar, 1999;Mitic et al, 2000). These junctions are dy-namic structures modulated by physiological and pathological conditions Cereijido et al, 2007). Changes in expression and intracellular localization of these TJ proteins are associated with alterations in paracellular transport (Balda et al, 2000;Coyne et al, 2003;Brooks et al, 2005Brooks et al, , 2006.…”

mentioning

confidence: 99%

Diclofenac Attenuates the Regional Effect of λ-Carrageenan on Blood-Brain Barrier Function and Cytoarchitecture

Nametz

Charles

Davis³

2008

J Pharmacol Exp Ther

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The microenvironment of the brain requires tight regulation for proper neuronal function. Protecting the central nervous system (CNS) from the varying concentrations of ions, proteins, and toxins in the periphery is the dynamically regulated blood-brain barrier (BBB). Recent studies have demonstrated significant modulation of the BBB in a number of diseases and physiological states, including pain. This study expands on previous explorations of acute and chronic pain-induced effects on the function and molecular cytoarchitecture of the barrier. It describes the role of cyclooxygenase (COX) up-regulation by blocking with diclofenac (30 mg/kg, i.p.), and it examines the variation in BBB regulation through various brain regions. Edema and hyperalgesia were induced by -carrageenan and attenuated by the additional administration of diclofenac. Examination of unidirectional [ 14 C]sucrose permeability with multitime in situ perfusion studies demonstrated that -carrageenan significantly increased cerebral permeability and decreased brainstem permeability. There were no significant changes in any of the other brain regions examined. These permeability changes correlated with up-and down-regulation of the tight junction (TJ) protein claudin-5 in the cerebrum and brainstem, respectively. Diclofenac administration attenuated the cerebral permeability uptake as well as the claudin-5 up-regulation. In addition, diclofenac reversed the lowered permeability in the brainstem, but it did not attenuate TJ protein expression. These studies demonstrate the complex regulation of the BBB occurring during inflammatory pain and the role of COX in this process. An understanding of BBB regulation during pain states is critically important for pharmacotherapy, and it holds great promise for new therapies to treat central nervous system pathologies.The central nervous system (CNS) is one of the most vital and delicate systems of the human body, requiring tight regulation. Ion and nutrient concentrations within the extracellular and interstitial fluid of the brain are precisely controlled. Independence from the peripheral circulation is essential for such control, protecting the CNS from fluctuation in ion concentrations, toxins, and the immune system. This environmental maintenance is carried out by the blood-CNS barrier, consisting of the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (Sharma et al., 2004). The BBB, situated at the level of endothelial tight junctions of cerebral microvessels (Reese and Karnovsky, 1967;Brightman et al., 1970), is critical for regulating and maintaining the brain microenvironment and, thus, proper neuronal function.The basis of the blood-brain barrier is the cerebral capillary endothelium with a continuous and large surface area that selectively allows passage into the CNS. The BBB endothelial cells are characterized by a lack of fenestrations, decreased pinocytosis, and the presence of tight junction (TJ) proteins, multiple transport systems, and enzymatic detoxification enzym...

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New Diseases Derived or Associated with the Tight Junction

Cited by 83 publications

References 121 publications

Ouabain modulates epithelial cell tight junction

Ouabain modulates epithelial cell tight junction

The Role of Intestinal Barrier Function in Early Life in the Development of Colitis

Diclofenac Attenuates the Regional Effect of λ-Carrageenan on Blood-Brain Barrier Function and Cytoarchitecture

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