Indinavir impairs protein synthesis and phosphorylations of MAPKs in mouse C2C12 myocytes

American Journal of Physiology. Cell Physiology
Ly Q Hong-BrownCharles H Lang

Abstract

Anti-retroviral therapy promotes clinical, immunologic, and virologic improvement in human immunodeficiency virus-infected patients. Whereas this therapy adversely affects carbohydrate and lipid metabolism, the effects of anti-retroviral drugs on muscle protein synthesis and degradation have not been reported. To examine these processes, we treated C2C12 myocytes with increasing concentrations of the protease inhibitor indinavir for 1 or 2 days. Treatment of myocytes with a therapeutic concentration of indinavir (20 microM) for 24 h decreased basal protein synthesis by 18%, whereas a 42% decline was observed after 48 h. A similar decrement, albeit quantitatively smaller, was detected with other protease inhibitors. Indinavir did not alter the rate of proteolysis. Likewise, indinavir did not impair the anabolic effect of insulin-like growth factor-I on protein synthesis. Mechanistically, indinavir decreased the phosphorylation of the S6 ribosomal protein (rpS6), and this reduction was associated with a decreased phosphorylation of p70S6 kinase and p90rsk as well as the upstream regulators ERK1/2 and MEK1/2. Indinavir also decreased the phosphorylation of Mnk1 and its upstream effectors, p38 MAPK and ERK1/2. Indinavir did not aff...Continue Reading

References

Feb 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·E Erikson, J L Maller
Feb 1, 1994·Current Opinion in Genetics & Development·C J Marshall
Jun 28, 1996·The Journal of Biological Chemistry·P LenormandJ Pouysségur
May 1, 1997·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·K MulliganM Schambelan
Jun 1, 1997·The EMBO Journal·H B JefferiesG Thomas
Jun 23, 1997·FEBS Letters·N Pullen, G Thomas
Feb 21, 1998·Science·N PullenG Thomas
Jul 20, 1999·Molecular and Cellular Endocrinology·M Frödin, S Gammeltoft
Dec 2, 1999·Experimental Cell Research·A Dufner, G Thomas
May 12, 2000·The Journal of Biological Chemistry·H MurataM Mueckler
Jun 29, 2000·Annual Review of Biochemistry·A C GingrasN Sonenberg
Aug 23, 2001·International Journal of STD & AIDS·J S Herman, P J Easterbrook
Oct 5, 2001·Alcoholism, Clinical and Experimental Research·L Q Hong-BrownC H Lang
Dec 13, 2001·AIDS·Richard Hodes
Mar 27, 2002·The Journal of Biological Chemistry·Masao SaitohGeorge Thomas
Mar 30, 2002·BMJ : British Medical Journal·Charles Carpenter
Apr 10, 2002·The Journal of Biological Chemistry·Yoshihiro IijimaDhandapani Kuppuswamy
Oct 12, 2002·American Journal of Physiology. Endocrinology and Metabolism·Vinayshree KumarCharles H Lang
Dec 31, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Michele L TurnerEdward P Acosta

❮ Previous
Next ❯

Citations

Jan 12, 2011·Pflügers Archiv : European journal of physiology·Victoria C FolettaAaron P Russell
Aug 11, 2006·Alcoholism, Clinical and Experimental Research·Ly Q Hong-BrownCharles H Lang
Jan 15, 2008·Biochemical and Biophysical Research Communications·Masuhiro NishimuraMuneharu Ikeda
Apr 14, 2005·American Journal of Physiology. Endocrinology and Metabolism·Ly Q Hong-BrownCharles H Lang
Oct 27, 2005·American Journal of Physiology. Endocrinology and Metabolism·Magali Prod'hommeJean Grizard
Jun 20, 2013·Rehabilitation Nursing : the Official Journal of the Association of Rehabilitation Nurses·Bernat-Carles Ferrer Serdà, Rafael Marcos-Gragera
Jun 13, 2020·Frontiers in Oncology·Giovanni Barillari
Jul 8, 2020·International Journal of Molecular Sciences·Giovanni Barillari

❮ 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.