JCI online early table of contents: May 8, 2008

Persistent high blood pressure (hypertension) puts an individual at increased risk of strokes, heart attacks, and heart failure. One cause of hypertension is decreased excretion of sodium in the urine, which increases the amount of sodium in the body fluids. This causes cells to release water, which increases blood pressure by accumulating in the blood and body fluids. The amount of sodium excreted in the urine is controlled by the response of the kidney to a number of hormones, some of which increase sodium excretion (e.g. dopamine) and some of which decrease it (e.g. Ang II). New data, generated in mice, by Pedro Jose and colleagues, at Georgetown University Medical Center, Washington, DC, have now shown that dopamine 5 receptor (D5R) negatively regulates expression of Ang II type 1 receptor (AT1R) such that the effects of changes in the expression and/or activity of D5R on blood pressure are compounded by changes in expression of AT1R. These data led the authors to suggest that targeting both or either of these receptors might be of benefit when designing approaches to optimize treatment for hypertension.

TITLE: Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells

AUTHOR CONTACT:
Pedro A. Jose
Georgetown University Medical Center, Washington, DC, USA.
Phone: (202) 444-8675; Fax: (202) 444-7161; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33637

BONE BIOLOGY: Specific role for one member of the NF-kappa-B family of proteins in bone cell development

New data, generated in mice by Deborah Novack and colleagues, at Washington University School of Medicine, St. Louis, have provided insight into the molecular pathways that regulate the development of bone cells known as osteoclasts, which function to reduce bone mass and are responsible for the bone loss associated with diseases such as osteoporosis and rheumatoid arthritis.

In the study, precursors of osteoclasts that lacked one member of the NF-kappa-B family of proteins (RelA) were impaired in their ability to develop into osteoclasts when stimulated with RANKL, a factor that usually induces osteoclast development. This defect in osteoclast development was due to increased death of the osteoclast precursors, induced by a RANKL-activated JNK-Bid cell-death pathway. Only the RelA NF-kappa-B family member was able to block this pathway, indicating that other family members cannot perform this function. These data, defining a specific role for RelA in allowing efficient osteoclast development, have implications when considering whether targeting NF-kappa-B family members would be beneficial to individuals with inflammatory diseases such as rheumatoid arthritis.

TITLE: RelA/p65 promotes osteoclast differentiation by blocking a RANKL-induced apoptotic JNK pathway in mice

AUTHOR CONTACT:
Deborah Veis Novack
Washington University School of Medicine, St. Louis, Missouri, USA.
Phone: (314) 454-8472; Fax: (314) 454-5047; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33392