CARDIOLOGY: Protecting heart muscle cells from death

A team of researchers, led by Uta Hoppe, at the University of Cologne, Germany, has identified a role for the protein connexin 43 in protecting mouse heart muscle cells from death. The team therefore suggest that it might be an attractive target for therapies that help protect cells from injuries that normally result in death, such as the injuries suffered by cells as a result of heart attack.

Several lines of evidence indicate that the PKC protein and mitoKATP potassium channels in the inner mitochondrial membrane have a central role in protecting cells from death. In the study, connexin 43 was found to be required for mitoKATP activation of PKC. Importantly, this pathway was crucial for protecting mouse heart muscle cells from death.

TITLE: Connexin 43 acts as a cytoprotective mediator of signal transduction by stimulating mitochondrial KATP channels in mouse cardiomyocytes

BACTERIOLOGY: Staph infections in the skin controlled by the immune molecule IL-17

In recent years, antibiotic-resistant strains of the bacterium Staphylococcus aureus, which is the most common cause of skin and soft tissue infections such as cellulitis, have emerged and are creating a serious public health concern. If we are to develop therapies that provide an alternative to antibiotics, greater understanding is needed of the immune response to Staphylococcus aureus skin infection. Lloyd Miller and colleagues, at the University of California at Los Angeles, have now provided new insight into this by studying a mouse model of the condition. Specifically, they found that the immune molecule IL-17 has an important role in controlling Staphylococcus aureus infection in the mouse skin. The authors therefore suggest that therapies aimed at inducing IL-17 responses in the skin may provide a new approach to treating individuals susceptible to Staphylococcus aureus skin infections.

TITLE: IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice

VACCINES: CD4+ immune cells control vaccinia virus, the smallpox vaccine

Immunization against smallpox was always considered successful if a skin lesion formed at the site of vaccination. As researchers are looking to use vaccinia virus, the virus in the smallpox vaccine, in other therapeutics and preventative vaccines, it is important to characterize more extensively the mechanisms by which the immune system controls vaccinia virus and thereby protects against smallpox. In this regard, Behazine Combadière and colleagues, at INSERM U945, France, have now determined that immune cells known as CD4+ T cells have an important role in controlling skin lesion size at sites of revaccination.

In the study, the number of effector CD4+ T cells targeting vaccinia virus that a person who was immunized against smallpox many years previously had in their blood prior to revaccination was the only immune correlate that determined the size of their skin lesion upon revaccination. Specifically, high numbers of these cells correlated with small skin lesion size upon revaccination. These data provide new insight into the mechanisms of immune control of vaccinia virus, highlighting a role for an immune cell not previously thought to be centrally involved in the process.

TITLE: Control of vaccinia virus skin lesions by long-term-maintained IFN-gamma+TNF-alpha+ effector/memory CD4+ lymphocytes in humans



CARDIOLOGY: Switching energy source in stressed hearts under the control of the protein Myc

When heart muscle cells are put under stress, for example by high blood pressure or by oxygen deprivation (such as occurs during a heart attack), they switch from using fatty acids as their source of energy to using glucose. Robb MacLellan and colleagues, at the David Geffen School of Medicine at UCLA, have now generated several lines of evidence to indicate that the gene regulatory protein Myc is responsible for inducing the expression of the genes involved in using glucose as an energy source in mice and that this helps protect the heart from stress.

Initial analysis by the authors indicated that expression of Myc was increased in the hearts of mice under conditions that model high blood pressure as well as conditions that model the oxygen deprivation associated with a heart attack. Furthermore, increasing Myc expression in the heart in the absence of any stress condition made the heart muscle cells switch from fatty acids to glucose as their source of energy. Importantly, the Myc-mediated switch to using glucose as an energy source was associated with preserving heart function and improving recovery from oxygen deprivation. Thus, Myc has an important adaptive role in the mouse heart, equipping it with an enhanced ability to respond to oxygen deprivation.

TITLE: Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice

Source:
Karen Honey
Journal of Clinical Investigation