High glucose induced translocation of Aquaporin8 to chicken hepatocyte plasma membrane: Involvement of cAMP, PI3K/Akt, PKC, MAPKs, and microtubule

Abstract

Aquaporin8 (AQP8) is a transmembrane water channel that is found mainly in hepatocytes. The direct involvement of AQP8 in high glucose condition has not been established. Therefore, this study examined the effects of high glucose on AQP8 and its related signal pathways in primary cultured chicken hepatocytes. High glucose increased the movement of AQP8 from the intracellular membrane to plasma membrane in a 30 mM glucose concentration and in a time- (> or =10 min) dependent manner. On the other hand, 30 mM mannitol did not affect the translocation of AQP8, which suggested the absence of osmotic effect. Thirty millimolar glucose increased intracellular cyclic adenosine 3, 5-monophosphate (cAMP) level. Moreover, high glucose level induced Akt phosphorylation, protein kinase C (PKC) activation, p44/42 mitogen-activated protein kinases (MAPKs), p38 MAPK, and c-jun NH2-terminal kinase (JNK) phosphorylation. On the other hand, inhibition of each pathway by SQ 22536 (adenylate cyclase inhibitor), LY 294002 (PI3-K phosphatidylinositol 3-kinase inhibitor), Akt inhibitor, staurosporine (PKC inhibitor), PD 98059 (MEK inhibitor), SB 203580 (p38 MAPK inhibitor), or SP 600125 (JNK inhibitor) blocked 30 mM glucose-induced AQP8 translocation, respectively. In addition, inhibition of microtubule movement with nocodazole blocked high glucose-induced AQP8 translocation. High glucose level also increased the level of kinesin light chain and dynein protein expression. In conclusion, high glucose level stimulates AQP8 via cAMP, PI3-K/Akt, PKC, and MAPKs pathways in primary cultured chicken hepatocytes.

Involvement of JNK/NFκB Signaling Pathways in the Lipopolysaccharide-Induced Modulation of Aquaglyceroporin Expression in 3T3-L1 Cells Differentiated into Adipocytes

“…TLR4 can activate the MAPK signaling pathway involving ERK, JNK and p38. ERK is activated in response to growth factors and intracellular calcium increases, for example, while JNK and p38 are activated by a variety of cellular oxidative stresses, such as inflammatory cytokines and heat shock proteins [51,52,53]. Activated JNK phosphorylates a variety of transcription factors which are involved in the formation and activation of the activator protein-1 (AP-1) complex [54].…”

Aquaporins in avian kidneys: function and perspectives

“…The presence of immunoreactive AQPs 2, 3, and 9 has been reported in gonadal accessory organs in turkeys (136,137). In chicken cultured hepatocytes, a high glucose level stimulates AQP8 via the cAMP, phosphatidylinositide 3-kinase (PI3-K)/Akt, PKC, and mitogen-activated protein kinases (MAPKs) pathways (114). Blood glucose levels are high in birds (16).…”

Interleukin‐6 promotes 2‐deoxyglucose uptake through p44/42 MAPKs activation via Ca2+/PKC and EGF receptor in primary cultured chicken hepatocytes

“…Therefore, the chicken hepatocyte is considered to be a target for IL-6 because hepatocytes are known to be major target cells for IL-6 in mammals. Primary hepatocyte cultures have been used in many biophysiological studies of liver function because they retain many liver-specific functions and respond to various hormones through the expression of liver-specific functions (Lee et al, 2006;Suh et al, 2008). The primary chicken hepatocytes culture system used in this study also retains the in vitro differentiated phenotype that is typical of the liver, including albumin expression (Hou et al, 2001), P450 1A induction (Hou et al, 2001), tyrosine aminotransferase expression (Sasaki et al, 2000), and ascorbate recycling (Sasaki et al, 2001).…”