Anisoosmotic Regulation of Hepatic Gene Expression

Abstract

The effect of anisoosmolarity on the abundance of various mRNA species was examined in perfused rat liver and H4IIE rat hepatoma cells. Hyperosmotic exposure (385 mosmol/l) of isolated rat livers increased mRNA levels for tyrosine aminotransferase (TAT) by 246% and those for phosphoenolpyruvate carboxykinase (PEPCK) by 186%, whereas hypoosmotic exposure (225 mosmol/l) decreased their levels to 43% and 42%, respectively. mRNA levels for fructose-1,6-bisphosphatase (FBP), argininosuccinate lyase (ASL), argininosuccinate synthetase (ASS), glutamine synthetase (GS), glutaminase (GA) and glucokinase (GK) were largely unaffected. In H4IIE cells the modulation of TAT and PEPCK mRNA levels by anisoosmotic exposure was similar to that found in perfused rat liver. ASL and glutaminase mRNA levels were influenced in an opposite manner. The effects of anisoosmolarity on PEPCK mRNA levels in H4IIE cells were largely abolished in the presence of the protein kinase inhibitors H-7, H-89 and H A-1004. Other protein kinase inhibitors such as Go-6850, KN-62, Rp-8-CPT-cAMPS, rapamycin, wortmannin, genistein or herbimycin did not prevent the osmosensitivity of PEPCK mRNA levels. Also pertussis and cholera toxin, vanadate and colchicine did not affect the osmosensitivity of PEPCK mRNA levels.The data suggest that anisoosmotic exposure acts on the levels of some but not all mRNA species and that this action may involve changes in protein phosphorylation. They further indicate that the recently identified osmosensitive signal transduction pathway which involves a G-protein and tyrosine kinase dependent activation of mitogen-activated protein kinases is apparently not involved in the osmoregulation of PEPCK mRNA levels.

Mal Mediates TLR-Induced Activation of CREB and Expression of IL-10

“…6B), suggesting a role for PKA. However, we were mindful that H89 has also been reported to act as an inhibitor of MSK2, a known upstream kinase of CREB, and thus, we also used Rp-8-CPT-cAMPs (Rp-8), a more selective inhibitor of PKA (39). However, Rp-8 failed to affect the ability of LPS to induce phosphorylation of CREB (Fig.…”

The Many Faces of H89: A Review

“…Rp-8-Br-cAMPS inhibits PKA effects in neuroblastoma (35) cells and Rp-8-CPT-cAMPS does not prevent the osmosensitivity of phosphoenolpyruvate carboxykinase (PEPCK), while the effects of anisoosmolarity on PEPCK mRNA were largely abolished by H89 (76). The relative membrane permeability of these Rp-cAMPS analogs vary greatly -from 1 (Rp-cAMPs) to 47.9 (Rp-8-HA-cAMPS) (5 …”

Hypoosmolarity and glutamine increased the β‐actin gene transcription in isolated rat hepatocytes

“…Thus, hypoosmolarity has been reported to increase the actin mRNA level in isolated rat hepatocytes [1], the argininosuccinate synthetase mRNA level in cultured rat hepatocytes [2] and the c-jun mRNA level in rat hepatoma cells [3]. Conversely, hypoosmolarity has been reported to decrease the phosphoenolpyruvate carboxykinase [4,5] and the tyrosine aminotransferase mRNA levels [5] in both perfused rat liver and H4IIE rat hepatoma cells. The opposite was observed in hyperosmotic conditions.…”