Targeted disruption of the nitric oxide synthase 2 gene protects against ischaemia/reperfusion injury to skeletal muscle

The Journal of Pathology
J E BarkerA G Stewart

Abstract

To provide definitive insight into the complicated roles of the nitric oxide synthase (NOS) enzymes in ischaemia/reperfusion (I/R) injury of skeletal muscle, experiments were undertaken in mice with targeted disruption of the inducible NOS (NOS-2 KO) isoform, compared with the wild-type mouse strain. The degree of I/R injury in the NOS-2 KO mice was attenuated relative to that in the wild-type strain. After 70 min of ischaemia (24 h reperfusion), nitroblue tetrazolium (NBT) staining of skeletal muscle showed significant necrosis (40%) in wild-type mice, whilst in NOS-2 KO mice, ischaemia could be prolonged to 90 min before significant necrosis (38%) was apparent. Specific enzyme activities of the mitochondrial respiratory chain enzymes, measured in skeletal muscle homogenates, suggested that direct inhibition of the enzymes is not causal in the I/R injury. Immunohistological examination of skeletal muscle for NOS-2 showed its induction selectively in mast cells. In vitro experiments using bone marrow-derived mast cells showed that NOS-2 induction was associated with increased degranulation of mast cells. These findings suggest that NO generated by induction of NOS-2 has a deleterious effect in I/R injury of skeletal muscle and ...Continue Reading

References

Oct 1, 1992·The Journal of Surgical Research·M J HickeyB M O'Brien
Jun 28, 1991·Biochemical and Biophysical Research Communications·E MasiniJ Vane
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J S BeckmanB A Freeman
Jan 17, 1985·The New England Journal of Medicine·J M McCord
Dec 8, 1994·Nature·L KobzikJ S Stamler
Jan 1, 1994·Microsurgery·L K KnoxW A Morrison
Jan 1, 1993·Microsurgery·C L Kerrigan, M A Stotland
Feb 23, 1996·Biochemical Pharmacology·G J Southan, C Szabó
Jan 1, 1996·Free Radical Biology & Medicine·J P BolañosJ B Clark
Nov 14, 1997·Physiological Reviews·D D MetcalfeY A Mekori
Aug 1, 1997·Biochemical Society Transactions·S J HealesJ P Bolaños
May 20, 1999·Annual Review of Pharmacology and Toxicology·A J HobbsS Moncada
Sep 1, 1999·International Journal of Experimental Pathology·K R KnightA G Stewart
Dec 22, 1999·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·E MasiniP F Mannaioni
Apr 1, 2000·Laboratory Investigation; a Journal of Technical Methods and Pathology·A MessinaA G Stewart
Aug 5, 2000·The Journal of Pathology·B LazarusK R Knight

❮ Previous
Next ❯

Citations

Jun 18, 2005·The Journal of Surgical Research·Achal KhannaRobert A Fitridge
Jan 7, 2003·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Paloma Martín-SanzLisardo Boscá
Sep 8, 2004·Nitric Oxide : Biology and Chemistry·Charan GowdaJames R Urbaniak
Jan 8, 2004·Acta Physiologica Hungarica·M Boros
Jun 8, 2004·Journal of Applied Physiology·Wen-Ning QiJames R Urbaniak
Feb 1, 2007·Anesthesiology·Mali MathruJohn D Lang
May 15, 2007·Immunological Reviews·Emily J Swindle, Dean D Metcalfe
Jun 9, 2004·Laboratory Investigation; a Journal of Technical Methods and Pathology·Susan K BortolottoAurora Messina
Dec 4, 2004·Plastic and Reconstructive Surgery·Steffen BaumeisterChristoph Heitmann
Dec 6, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lorenz SchildWolfgang Augustin
Dec 31, 2002·Journal of Applied Physiology·Li ZhangJames R Urbaniak
Aug 5, 2004·Journal of Neuropathology and Experimental Neurology·N C JonesS Murphy
Apr 15, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Roy W R DudleyBasil J Petrof
Apr 19, 2021·Nanomedicine : Nanotechnology, Biology, and Medicine·Louis HinkleSuchismita Acharya
Jul 25, 2021·International Journal of Molecular Sciences·George ClarkeDarius F Mirza

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.