Juan Sastre Ph.D. Professor of Physiology at the University of Valencia, SpainJuan Sastre was born in Valencia, Spain, in 1963. He graduated in Pharmacy at the University of Valencia, and obtained his PhD in 1989 doing a Doctoral Thesis on oxidative stress and aging of the liver supervised by Prof. José Viña and Prof. Federico V. Pallardó. After staying in the Human Nutrition Research Center on Aging at Tufts University (Boston, USA), King’s College London (UK), and Unité INSERM 99 at the Hôpital Henri Mondor (France), he returned to the Department of Physiology of the University of Valencia to work first as Assistant Professor and later as Titular Professor. He has teaching experience in Human Physiology from 1987, in Human Pathophysiology from 1998, and in Hematology from 2003 to date.Juan Sastre is Full Professor at the University of Valencia since 2006 and his research work focuses on the role of oxidative stress and redox signaling in Gastroenterology, particularly in acute pancreatitis and liver cirrhosis. He has published more than 150 papers on oxidative stress, glutathione, antioxidants, mitochondria, aging, apoptosis, cytokines, protein phosphatases, redox signaling, histone acetylation, acute pancreatitis, and secondary biliary cirrhosis. He has obtained different awards for his research work: “Catherine Pasquier Memorial Award 2005” given by the Society for Free Radical Research (Europe) for his relevant scientific achievements in the area of free radical research; “Harwood Young Investigator Award” for free radical research 1998, given by the Society for Free Radical Research (Europe); and “García Blanco” medal in 1992 given to young researchers in Biomedicine by the School of Medicine of Valencia (Spain). Juan Sastre was General Secretary of SFRR-Europe from 2013 till 2020, and presently is President Elect of SFRR-E.
We have studied experimental acute pancreatitis as a model of acute inflammation. It is an inflammatory disorder of the pancreas that eventually may lead to the syndrome of systemic inflammatory response, and in severe cases to death by multiorgan failure. One of the early key features of pancreatic injury is glutathione depletion, which is transient in mild pancreatitis but it is maintained for a long time in severe pancreatitis due to inefficient induction of glutamate cysteine ligase. In addition, blockade of the transsulfuration pathway is produce by nitration of cystathionine b-synthase. It should be also highlighted that pancreatic inflammation is also associated with protein cysteinylation, but not with protein glutathionylation nor glutathione oxidation, leading to disulfide stress. We have identified two types of targets of disulfide stress, on the one hand redox buffers, such as ribonuclease inhibitor and albumin; and on the other hand redox signaling through thiols that involve tyrosine and serin/threonine phosphatases, which markedly affects the inflammatory cascade. The enzymatic regulation of protein cysteinylation has been elucidated. The inflammatory cascade is algo regulated by PGC-1a, which forms a complex with the subunit p65 of NF-kB. This inhibitory complex reduces specifically the up-regulation of interleukin 6, which triggers pulmonary infiltration and injury and infiltrate. Obesity causes a marked deficiency in PGC-1a in the pancreas promoting pulmonary damage in acute pancreatitis. Later in the course of acute pancreatitis, p53 induces necroptosis in acinar cells through the loss of sulfiredoxin and mitochondrial peroxiredoxin 3. In conclusion, maintained glutathione depletion together with disulfide stress, PGC-1a deficiency, y and necroptosis induced by p53 decisively contribute to severity in acute pancreatitis.