Endotoxin unmasks the role of gap junctions in the liver

Correa, Paulo Renato A.V.; Guerra, Mateus T.; Leite, M. Fátima; Spray, David C.; Nathanson, Michael H.

doi:10.1016/j.bbrc.2004.07.192

Cited by 21 publications

(21 citation statements)

References 51 publications

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“…albumin) acute phase transcripts were observed following administration of cytokines and LPS to Cx32-deficient mice compared with wild-type mice, suggesting that Cx32 does not play a role in experimental liver inflammation [55]. Correa and colleagues showed that Cx32-based gap junctions are indispensable in model animals during the recovery from hypoglycemia and cholestasis upon LPS-triggered systemic inflammation [56]. On the other hand, increases in serum ALT and AST levels and the occurrence of cell death were less manifested in Cx32 dominant-negative mutant transgenic rats that received carbon tetrachloride in comparison with their wild-type counterparts, pointing to a role for GJIC in the dissemination of cell injury and cell death signals [74].…”

Section: Discussionmentioning

confidence: 96%

“…", upregulation; ;, downregulation; $, no modification. Liver tissue from chronic hepatitis patients ↓ Cx32 protein [40] ↓ Cx32 protein Cx32 in cytoplasm [39] Liver tissue from rats treated with LPS ↓ GJIC ↓ Cx32 protein [56] ↓ Cx32 protein ↓ Cx32 mRNA (degradation) [57] ↓ Cx32 mRNA (degradation/shortening poly(A) tail) [59] ↓ Cx26 protein ↓ Cx32 protein ↑ Cx43 protein [31] ↑ Gap junctions (Kupffer cells) [61] Isolated perfused liver from rats treated with LPS ↓ GJIC ↓ Cx26 protein ↑ Cx26 mRNA ↓ Cx32 protein ↓ Cx32 mRNA [58] Liver tissue from mice treated with LPS/TNFα/IL-1β/IL-2/IL-6 ↑ Cx26 mRNA/protein (LPS/TNFα) Cx26 mRNA/protein (IL-1β/IL-2/IL-6) ↓ Cx32 protein (LPS/TNFα/IL-1β/IL-2/IL-6) ↓ Cx32 mRNA (LPS)…”

Section: Conflict Of Interestmentioning

confidence: 97%

“…An acute status of inflammation can be experimentally induced in animals by injection of lipopolysaccharide (LPS), a component isolated from the outer membrane of Gram-negative bacteria that acts as an endotoxin. Similar to hepatitis patients, decreased liver Cx32 amounts have been measured in mice [55] and rats [31,56,57] as well as in isolated perfused livers [58] treated with LPS. This is paralleled by identical changes at the mRNA level [55,[57][58][59], which in turn results from increased Cx32 mRNA degradation [57,59] by shortening of its poly(A) tail [59].…”

Section: Gap Junctions In Hepatitis and Systemic Inflammationmentioning

confidence: 98%

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Gap junctions and non-neoplastic liver disease

Vinken

2012

Journal of Hepatology

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Because of their critical role as goalkeepers of hepatic homeostasis, gap junctions are frequent targets in liver disease. This concept has been demonstrated on many occasions in the light of hepatocarcinogenesis. Relatively little focus has been put on the fate of gap junctions in other liver pathologies, including hepatitis, liver fibrosis and cirrhosis, cholestasis and hepatic ischemia and reperfusion injury. The present paper provides an in-depth description of the multiple changes in expression, localization and function of connexins, the molecular constituents of gap junctions. The use of connexins as biomarkers and therapeutic targets in liver disease is also illustrated.

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Section: Discussionmentioning

confidence: 96%

Section: Conflict Of Interestmentioning

confidence: 97%

Section: Gap Junctions In Hepatitis and Systemic Inflammationmentioning

confidence: 98%

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Gap junctions and non-neoplastic liver disease

Vinken

2012

Journal of Hepatology

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“…Cx32 and Cx26, two parenchymal cells Cxs, are reduced in acute liver inflammation induced by LPS (5,(23)(24)(25)(26), hepatic ischemia/ reperfusion (25), and cholestasis caused by common bile duct ligation (5,27). Under these conditions the expression of Cx43 by KCs, non-parenchymal cells, is enhanced to clear/repair the damage.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro

Eugenín

González

Sánchez

et al. 2007

Cellular Immunology

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Connexin43 (Cx43), a gap junction protein subunit, has been previously detected in Kupffer cells (KCs) during liver inflammation, however, KCs phagocytose cell debris that may include Cx43 protein, which could explain the detection of Cx43 in KCs. We determined that KCs express Cx43 and form gap junctions both in vivo and in vitro. In liver sections of animals treated with LPS, Cx43 was detected at ED2+ cells interfaces, indicating formation of GJ between KCs in vivo. In vitro, unstimulated KCs cultures did not form functional GJs, and expressed low levels of Cx43 that showed a diffuse intracellular distribution. In contrast, KCs treated with LPS plus IFN-γ, expressed a greater amount of Cx43 at both the, protein and mRNA levels, and showed Cx43 at cell-cell contacts associated with higher dye coupling. In conclusion, activation of KCs in vivo or in vitro resulted in enhanced Cx43 expression levels and formation of GJ that might play relevant roles during liver inflammation.

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“…Regardless of the receptor used, it is now clear that PGF 2␣ , in addition to G q -mediated Ins(1,4,5)P 3 generation, can activate other signal transduction systems (20) that may be involved in GJP inhibition (17). This inhibitory effect may be involved in the inhibition of GJP observed in many pathological conditions, particularly during inflammation (10,12,13,18,43).…”

Section: Effect Of Long-term Perfusion Of Pgf 2␣ and Pge 2 On Ca 2ϩ Rmentioning

confidence: 96%

Effects of the prostaglandins PGF_2αand PGE₂on calcium signaling in rat hepatocyte doublets

Koukoui¹,

Boucherie²,

Sezan³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Coordination of intercellular Ca2+ signals is important for certain hepatic functions including biliary flow and glucose output. Prostaglandins, such as PGF2alpha and PGE2, may modify these hepatocyte functions by inducing Ca2+ increase, but very little is known about the organization of the Ca2+ signals induced by these agonists. We studied Ca2+ signals induced by PGF2alpha and PGE2 in fura-2 AM-loaded hepatocyte doublets. Even though both prostaglandins induced Ca2+ oscillations, neither PGF2alpha nor PGE2 induced coordinated Ca2+ oscillations in hepatocyte doublets. Gap junction permeability (GJP), assessed by fluorescence recovery after photobleaching, showed that this absence of coordination was not related to a defect in GJP. Inositol (1,4,5)trisphosphate [Ins(1,4,5)P3] assays and the increase in Ins(1,4,5)P3 receptor sensitivity to Ins(1,4,5)P3 observed in response to thimerosal suggested that the absence of coordination was a consequence of the very small quantity of Ins(1,4,5)P3 formed by these prostaglandins. Furthermore, when PGE2 and PGF2alpha were added just before norepinephrine, they favored the coordination of Ca2+ signals induced by norepinephrine. However, GJP between hepatocyte doublets was strongly inhibited by prolonged (>or=2 h) treatment with PGF2alpha, thereby preventing the coordination of Ca2+ oscillations induced by norepinephrine in these cells. Thus, depending on the time window, prostaglandins, specially PGF2alpha, may enhance or diminish the propagation of Ca2+ signals. They may therefore contribute to the fine tuning of Ca2+ wave-dependent functions, such as nerve stimulation, hormonal regulation of liver metabolism, or bile secretion, in both normal and pathogenic conditions.

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Endotoxin unmasks the role of gap junctions in the liver

Cited by 21 publications

References 51 publications

Gap junctions and non-neoplastic liver disease

Gap junctions and non-neoplastic liver disease

Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro

Effects of the prostaglandins PGF_2αand PGE₂on calcium signaling in rat hepatocyte doublets

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Endotoxin unmasks the role of gap junctions in the liver

Cited by 21 publications

References 51 publications

Gap junctions and non-neoplastic liver disease

Gap junctions and non-neoplastic liver disease

Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro

Effects of the prostaglandins PGF2αand PGE2on calcium signaling in rat hepatocyte doublets

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Product

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Effects of the prostaglandins PGF_2αand PGE₂on calcium signaling in rat hepatocyte doublets