RxPG News Feed for RxPG News

Medical Research Health Special Topics World
 Asian Health
 Food & Nutrition
 Men's Health
 Mental Health
 Occupational Health
 Public Health
 Sleep Hygiene
 Women's Health
 Canada Healthcare
 China Healthcare
 India Healthcare
 New Zealand
 South Africa
 World Healthcare
   Latest Research
 Alternative Medicine
   Multiple Myeloma
   Non-Hodgkin's Lymphoma
  Bone Cancer
  Breast Cancer
  Cervical Cancer
  Gastric Cancer
  Liver Cancer
  Nerve Tissue
  Ovarian Cancer
  Pancreatic Cancer
  Prostate Cancer
  Rectal Cancer
  Renal Cell Carcinoma
  Risk Factors
  Testicular Cancer
 Clinical Trials
 Infectious Diseases
 Sports Medicine
   Medical News
 Awards & Prizes
   Special Topics
 Odd Medical News

Last Updated: Oct 11, 2012 - 10:22:56 PM
Research Article
Blood Channel

subscribe to Blood newsletter
Latest Research : Cancer : Blood

   EMAIL   |   PRINT
HO-1 in sickle cell disease

Jul 19, 2006 - 3:33:00 AM , Reviewed by: Sanjukta Acharya

[RxPG] Rochester, Minnesota -- Researchers have unexpectedly shown that sickle cell-associated kidney injury may be reduced by inhibiting the enzyme activity of a protein that commonly confers protection in other diseased states. The paper by Juncos et al., "Anomalous renal effects of tin protoporphyrin in a murine model of sickle cell disease," appears in the July issue of The American Journal of Pathology.

Sickle cell disease (SCD), which affects greater than 70,000 individuals in the US, is an inherited hemoglobin disorder that causes some red blood cells to lose their smooth round shape and assume a crescent, or sickle, shape. Sickle cells can become lodged in small capillary blood vessels, with blockage of blood flow leading to pain, stroke, and damage to most organs including the lungs, spleen, kidneys and liver.

The mechanisms underlying SCD-associated kidney disease include various forms of secondary stress, such as changes in internal kidney blood flow, induction of oxidative injury, and influx of inflammatory cells. Researchers have thought that cells combat such stress through expression of heme oxygenase-1 (HO-1), a protective enzyme that is upregulated in SCD kidneys in humans and in mouse models. New research, however, suggests that in SCD HO-1 may not be as protective as previously thought.

In an attempt to understand the specific role of HO-1 in kidney injury, Juncos et al. examined SCD mice in the presence or absence of tin protoporphyrin (SnPP), a widely accepted inhibitor of the enzyme activity of HO. Short-term SnPP treatment successfully blocked HO activity in both normal and SCD mice, reduced kidney blood flow in normal and SCD mice, but did not affect the filtration capacity of the kidney in either group. However, when chronically administered, SnPP caused inflammation and fibrosis (scarring) in normal mice but not in SCD mice; in normal mice, SnPP induced genes related to fibrosis and inflammation, whereas in SCD mice, these genes were downregulated.

The scientists next examined the effect of SnPP on kidney injury induced by temporarily interrupting kidney blood flow (ischemia); the kidney in SCD mice is hypersensitive to such ischemia. Surprisingly, when mice were treated with SnPP, SCD kidneys were protected from ischemia-induced cell death and blood vessel blockage whereas normal kidneys exhibited cell death and injury. Thus, in contrast with its effects observed in normal mice, SnPP protected SCD kidneys from injury.

In other diseases, induction of HO-1 is protective by generating products such as carbon monoxide and bile pigments, both of which can reduce tissue injury; however, in larger amounts, these products may be toxic. It is possible that the degree of induction of HO-1 in SCD may generate toxic rather than protective amounts of these products. Additionally, along with its intended effect of inhibiting HO activity, SnPP may induce HO-1 protein, and this latter effect may underlie the observed cytoprotection. Finally, besides inhibiting HO activity, SnPP may concomitantly interrupt other pathways, independent of the HO system, that contribute to kidney injury in SCD.

In the process of analyzing the biologic significance of HO-1 in SCD, Juncos et al. uncovered an experimental strategy that reduced kidney injury in a mouse model of SCD. Further work will likely delineate the basis for the protective effects of SnPP in SCD, specifically, the dependency on inhibition of HO activity, increase in HO-1 protein, or some other as-yet-undefined mechanism.

Publication: American Journal of Pathology

Advertise in this space for $10 per month. Contact us today.

Related Blood News

Subscribe to Blood Newsletter

Enter your email address:

 Additional information about the news article
This work was supported by the National Institutes of Health.

Work was directed by Dr. Karl Nath from the Mayo Clinic College of Medicine and involved collaboration with the University of Minnesota.
Juncos JP, Grande JP, Murali N, Croatt AJ, Juncos LA, Hebbel RP, Katusic ZS, Nath KA. Anomalous renal effects of tin protoporphyrin in a murine model of sickle cell disease. Am J Pathol 2006 169:21-31

The American Journal of Pathology, the official journal of the American Society for Investigative Pathology (ASIP), seeks to publish high-quality original papers on the cellular and molecular mechanisms of disease. The editors accept manuscripts which report important findings on disease pathogenesis or basic biological mechanisms that relate to disease, without preference for a specific method of analysis. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, biological, animal, chemical and immunological approaches in conjunction with morphology
For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

Contact us

RxPG Online



    Full Text RSS

© All rights reserved by RxPG Medical Solutions Private Limited (India)