The contribution of necroptosis and apoptosis during acute kidney injury

• Grant number: 08/09773-4
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2009
• End date: February 28, 2011
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Júlio César Martins Monte
• Grantee: Júlio César Martins Monte
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Acute kidney injury involves two key mechanisms, namely necrosis and apoptosis, the former representing a non-specific, unregulated form of cell death, whilst the latter is a highly regulated process designed to systematically dismantle damaged cells and maintain homeostasis. The participation of an ever-growing number of molecules in the apoptotic machinery offers a plethora of opportunities for apoptosis modulation. Caspase inhibition have provided valuable efficacy in inhibiting apoptotic cell death in different models of injury, including cerebral, cardiac e kidney.However, the success of anti-apoptotic therapies has been limited, perhaps because of our lack of understanding of complexity of cell death regulation in mammalian cells. Emerging evidence suggests that apoptosis is not the only mechanism of cellular suicide, but rather that cells might choose necroptosis as a mechanism to die. Necroptosis represents a type of non apoptotic cell death mechanism. If several mechanisms are operational, then a combination therapy might provide maximal benefit. In this study, we aim to study the effect of necrostatin-1, which blocks a critical step in necroptosis, in the setting of model of toxic kidney injury by cisplatin and evaluate cytoprotective treatment by combination therapy (anti-apoptotic and anti-necroptotic) (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TRISTAO, VIVIAN REGINA; GONCALVES, PAULA FERNANDA; DALBONI, MARIA APARECIDA; BATISTA, MARCELO COSTA; DURAO, JR., MARCELINO DE SOUZA; MARTINS MONTE, JULIO CESAR. Nec-1 Protects against Nonapoptotic Cell Death in Cisplatin-Induced Kidney Injury. RENAL FAILURE, v. 34, n. 3, p. 373-377, 2012. (08/09773-4)

TRISTAO, VIVIAN REGINA; PESSOA, EDSON A.; NAKAMICHI, RENATA; REIS, LUCIANA A.; BATISTA, MARCELO COSTA; DURAO JUNIOR, MARCELINO DE SOUZA; MARTINS MONTE, JULIO CESAR. Synergistic effect of apoptosis and necroptosis inhibitors in cisplatin-induced nephrotoxicity. Apoptosis, v. 21, n. 1, p. 51-59, JAN 2016. (08/09773-4)