Cardiac myocyte-specific knock-out of calcium-independent phospholipase A2γ (iPLA2γ) decreases oxidized fatty acids during ischemia/reperfusion and reduces infarct size

Calcium-independent phospholipase A(2)γ (iPLA(2)γ) is a mitochondrial enzyme that produces lipid second messengers that facilitate opening of the mitochondrial permeability transition pore (mPTP) and contribute to the production of oxidized fatty acids in myocardium. To specifically identify the roles of iPLA(2)γ in cardiac myocytes, we generated cardiac myocyte-specific iPLA(2)γ knock-out (CMiPLA(2)γKO) mice by removing the exon encoding the active site serine (Ser-477). Hearts of CMiPLA(2)γKO mice exhibited normal hemodynamic function, glycerophospholipid molecular species composition, and normal rates of mitochondrial respiration and ATP production. In contrast, CMiPLA(2)γKO mice demonstrated attenuated Ca(2+)-induced mPTP opening that could be rapidly restored by the addition of palmitate and substantially reduced production of oxidized polyunsaturated fatty acids (PUFAs). Furthermore, myocardial ischemia/reperfusion (I/R) in CMiPLA(2)γKO mice (30 min of ischemia followed by 30 min of reperfusion in vivo) dramatically decreased oxidized fatty acid production in the ischemic border zones. Moreover, CMiPLA(2)γKO mice subjected to 30 min of ischemia followed by 24 h of reperfusion in vivo developed substantially less cardiac necrosis in the area-at-risk in comparison with their WT littermates. Furthermore, we found that membrane depolarization in murine heart mitochondria was sensitized to Ca(2+) by the presence of oxidized PUFAs. Because mitochondrial membrane depolarization and calcium are known to activate iPLA(2)γ, these results are consistent with salvage of myocardium after I/R by iPLA(2)γ loss of function through decreasing mPTP opening, diminishing production of proinflammatory oxidized fatty acids, and attenuating the deleterious effects of abrupt increases in calcium ion on membrane potential during reperfusion

Genetic deletion of skeletal muscle iPLA2γ results in mitochondrial dysfunction, muscle atrophy and alterations in whole-body energy metabolism

Skeletal muscle is the major site of glucose utilization in mammals integrating serum glucose clearance with mitochondrial respiration. To mechanistically elucidate the roles of iPL

Robots and cyborgs: to be or to have a body?

Starting with service robotics and industrial robotics, this paper aims to suggest philosophical reflections about the relationship between body and machine, between man and technology in our contemporary world. From the massive use of the cell phone to the robots which apparently “feel” and show emotions like humans do. From the wearable exoskeleton to the prototype reproducing the artificial sense of touch, technological progress explodes to the extent of embodying itself in our nakedness. Robotics, indeed, is inspired by biology in order to develop a new kind of technology affecting human life. This is a bio-robotic approach, which is fulfilled in the figure of the cyborg and consequently in the loss of human nature. Today, humans have reached the possibility to modify and create their own body following their personal desires. But what is the limit of this achievement? For this reason, we all must question ourselves whether we have or whether we are a body

Engineers of Life? A Critical Examination of the Concept of Life in the Debate on Synthetic Biology

The concept of life plays a crucial role in the debate on synthetic biology. The first part of this chapter outlines the controversial debate on the status of the concept of life in current science and philosophy. Against this background, synthetic biology and the discourse on its scientific and societal consequences is revealed as an exception. Here, the concept of life is not only used as buzzword but also discussed theoretically and links the ethical aspects with the epistemological prerequisites and the ontological consequences of synthetic biology. The second part examines this point of intersection and analyses some of the issues which are discussed in terms of the concept of life. The third part turns to the history of the concept of life. It offers an examination of scientific and philosophical discourses on life at the turn of the 20th century and suggests a surprising result: In the light of this history, synthetic biology leads to well-known debates, arguments, notions and questions. But it is concluded that the concept of life is too ambiguous and controversial to be useful for capturing the actual practice of synthetic biology. In the fourth part I argue that with regard to the ethical evaluation of synthetic biology, the ambiguity of the concept of life is not as problematic as sometimes held because other challenges are more important. The question whether the activity of synthetic biological systems should be conceived as life or not is primarily theoretical