Vesicular ATP release from hepatocytes plays a role in the progression of nonalcoholic steatohepatitis.

Vesicular ATP release from hepatocytes plays a role in the progression of nonalcoholic steatohepatitis. Biochim Biophys Acta Mol Basis Dis. 2020 Nov 16;:166013 Authors: Tatsushima K, Hasuzawa N, Wang L, Hiasa M, Sakamoto S, Ashida K, Sudo N, Moriyama Y, Nomura M Abstract Non-alcoholic steatohepatitis (NASH) is becoming a growing public health problem along with the increase of metabolic syndrome worldwide. Extracellular nucleotides are known to serve as a danger signal by initiating purinergic signaling in many inflammatory disorders, although the role of purinergic signaling in the progression of NASH remains to be clarified. Vesicular nucleotide transporter (VNUT) is a key molecule responsible for vesicular ATP release to initiate purinergic signaling. Here, we studied the role of VNUT in the progression of nonalcoholic steatohepatitis. VNUT was expressed in mouse hepatocytes and associated, at least in part, with apolipoprotein B (apoB)-containing vesicles. High glucose stimulation evoked release of appreciable amount of ATP from hepatocytes, which disappeared in hepatocytes of Vnut knockout (Vnut-/-) mice. Glucose treatment also stimulated triglyceride secretion from hepatocytes, which was inhibited by PPADS and MRS211, antagonists of P2Y receptors, and clodronate, a VNUT inhibitor, and was significantly reduced in Vnut-/- mice. In vivo, postprandial secretion of triglyceride from hepatocytes was observed, while the serum triglyc...
Source: Acta Med Okayama - Category: Universities & Medical Training Authors: Tags: Biochim Biophys Acta Mol Basis Dis Source Type: research