Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is proposed that gallstones stem from insufficiency of micronutrient antioxidants relative to the load of oxidants and/or oxidation-prone substrates within hepatocytes in such a way that ancillary hepatobiliary resources, including bilirubin with lactoferrin and mucin, are mobilized to combat oxidative stress but inadvertently promote lithogenesis. Aberrant activities of hepatic cytochrome P450 mono-oxygenases and of haem oxygenase are integral to this template, because differential inhibition or activation of these enzymes would help to rationalize the spectrum of human gallstone composition and also the different outcomes when animals are fed the same lithogenic diets. The hypothesis is based on a decade of work on another lithogenic disease, chronic pancreatitis. It accommodates observations on human and experimental gallstones, it is testable and, as shown by studies of chronic pancreatitis, has implications for primary disease prevention.
 ...
PMID:A radical view of gallstone aetiogenesis. 874 97

Upon injury, prolonged inflammation and oxidative stress may cause pathological wound healing and fibrosis, leading to formation of excessive scar tissue. Fibrogenesis can occur in most organs and tissues and may ultimately lead to organ dysfunction and failure. The underlying mechanisms of pathological wound healing still remain unclear, and are considered to be multifactorial, but so far, no efficient anti-fibrotic therapies exist. Extra- and intracellular levels of free heme may be increased in a variety of pathological conditions due to release from hemoproteins. Free heme possesses pro-inflammatory and oxidative properties, and may act as a danger signal. Effects of free heme may be counteracted by heme-binding proteins or by heme degradation. Heme is degraded by heme oxygenase (HO) that exists as two isoforms: inducible HO-1 and constitutively expressed HO-2. HO generates the effector molecules biliverdin/bilirubin, carbon monoxide, and free iron/ferritin. HO deficiency in mouse and man leads to exaggerated inflammation following mild insults, and accumulating epidemiological and preclinical studies support the widely recognized notion of the cytoprotective, anti-oxidative, and anti-inflammatory effects of the activity of the HO system and its effector molecules. In this review, we address the potential effects of targeted HO-1 induction or administration of HO-effector molecules as therapeutic targets in fibrotic conditions to counteract inflammatory and oxidative insults. This is exemplified by various clinically relevant conditions, such as hypertrophic scarring, chronic inflammatory liver disease, chronic pancreatitis, and chronic graft rejection in transplantation.
 ...
PMID:Heme oxygenase, inflammation, and fibrosis: the good, the bad, and the ugly? 2258 96