Rat Liver Enzyme Release Depends on Blood Flow-Bearing Physical Forces Acting in Endothelium Glycocalyx rather than on Liver Damage.
We have found selective elevation of serum enzyme activities in rats subjected to partial hepatectomy (PH), apparently controlled by hemodynamic flow-bearing physical forces. Here, we assess the involvement of stretch-sensitive calcium channels and calcium mobilization in isolated livers, after chemical modifications of the endothelial glycocalyx and changing perfusion directionality. Inhibiting in vivo protein synthesis, we found that liver enzyme release is influenced by de novo synthesis of endothelial glycocalyx components, and released enzymes are confined into a liver "pool." Moreover, liver enzyme release depended on extracellular calcium entry possibly mediated by stretch-sensitive calcium channels, and this endothelial-mediated mechanotransduction in liver enzyme release was also evidenced by modifying the glycocalyx carbohydrate components, directionality of perfusing flow rate, and the participation of nitric oxide (NO) and malondialdehyde (MDA), leading to modifications in the intracellular distribution of these enzymes mainly as nuclear enrichment of "mitochondrial" enzymes. In conclusion, the flow-induced shear stress may provide fine-tuned control of released hepatic enzymes through mediation by the endothelium glycocalyx, which provides evidence of a biological role of the enzyme release rather to be merely a biomarker for evaluating hepatotoxicity and liver damage, actually positively influencing progression of liver regeneration in mammals.
División de Ciencias Biológicas y de la Salud, Departamento de Atención a la Salud, Universidad Autónoma Metropolitana (UAM Xochimilco), 04960 Ciudad de México, Mexico.
Julieta A
JA
Díaz-Juárez
Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), 04510 Ciudad de México, Mexico.
Rolando
0000-0002-5010-775X
R
Hernández-Muñoz
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005969:Glutamate Dehydrogenase / Q000097:blood; D019276:Glycocalyx / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000293:injuries / Q000601:surgery*; D008291:Malate Dehydrogenase / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D033081:Shear Strength
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009569:Nitric Oxide; D008315:Malondialdehyde; D008291:Malate Dehydrogenase; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002118:Calcium