The highs and lows of stress in the heart

Regulation of cardiac gene expression by c-Jun N-terminal kinase (JNK) vs p38-MAPK signalling in response to oxidative stresses

Heart muscle cells work hard to pump blood through the body and are subjected to a number of stresses, including oxidative stresses, where high levels of molecules called reactive oxygen species can cause death of heart muscle cells. This can occur after a heart attack or in heart failure. On the other hand, low levels of oxidative stress set off a protective programme that enables the heart to withstand subsequent stress. These responses are managed by changes in the genes expressed by the heart. This PhD studentship project investigates two key systems that operate in the heart in response to oxidative stress, JNKs and p38-MAPKs. Activation of these pathways may be beneficial at low level oxidative stress, but are potentially damaging with high level oxidative stress. Inhibitors of each system will be used to determine whether/when they are damaging and how they exert their effects. The information will indicate whether inhibiting JNKs or p38-MAPKs may be beneficial for the heart and will identify genes that control heart muscle survival or death.