Heme oxygenase isoform-specific expression and distribution in the rat kidney

Abstract

These results suggest that HO-2 is constitutively expressed in the rat kidney mainly within tubular and arteriolar structures, and its activity may modulate physiological function under basal conditions. On the other hand, the basal levels of expression of HO-1 in the rat kidney are relatively low, and its contribution to HO activity and the regulation of hemoproteins such as cytochrome P450 become apparent only under pathophysiological conditions causing HO induction.

Thrombomodulin domain 1 ameliorates diabetic nephropathy in mice via anti-NF-κB/NLRP3 inflammasome-mediated inflammation, enhancement of NRF2 antioxidant activity and inhibition of apoptosis

“…It is established that expression levels or the activity of HO-1 and GPx are involved in the elimination or inactivation of ROS [35], and that this effect is mediated by activation of NRF2 [36]. Although normal tissues express extremely low basal levels of HO-1 protein [37,38], diabetic rats receiving antioxidant treatment have significantly increased HO-1 protein levels compared with normal controls [39]. Together, our data suggest that the expression of HO-1 protein may be a key factor in preventing mice from developing renal lesions in DN.…”

Heme Oxygenase-2 Deficiency Contributes to Diabetes-Mediated Increase in Superoxide Anion and Renal Dysfunction

“…Furthermore, da Silva et al (5) showed that HO-2 is expressed at different levels within renal structure, and its distribution regulates many heme proteins, such as cyclooxygenase, nitric oxide synthase, and thromboxane synthase.…”

“…HO-1 and HO-2, the inducible and constitutive HO forms, respectively, play an important role in maintaining renal blood flow (4). HO-2 expression along the nephron follows regional distributions, the highest levels being detected in the medullary thick ascending limb and proximal tubules (5)(6)(7). It plays a regulatory role in renal cytochrome P450 expression and 20-hydroxyeicosatetraenoic acid synthesis; the latter regulates renal function and vascular response (8 -12).…”

Physiology and Pathophysiology of Heme

“…HO-1 is the isozyme that is upregulated in stressed organs and tissues, and is induced by a diverse array of stimuli, including hypoxia, ischemia, hyperoxia, oxidative stress, proinflammatory stress, and heavy metals. HO-1 is expressed weakly in renal tubules in the unstressed kidney but can be induced strongly in renal tubules and arterioles by stressors such as heme and certain metals (22). HO-2 is the constitutive isozyme that accounts for the bulk of HO activity in the kidney in health and is expressed in the preglomerular vasculature, the thick ascending limb, and the distal nephron (22).…”

“…HO-1 is expressed weakly in renal tubules in the unstressed kidney but can be induced strongly in renal tubules and arterioles by stressors such as heme and certain metals (22). HO-2 is the constitutive isozyme that accounts for the bulk of HO activity in the kidney in health and is expressed in the preglomerular vasculature, the thick ascending limb, and the distal nephron (22). The induction of HO-1, at least in distal nephron-derived cells, is more robust after basolateral as compared with apical exposure to heme, and such induction is accentuated by pathophysiologically relevant stimuli such as hypoxia and hepatocyte growth factor (23).…”