Nitric oxide can inhibit apoptosis or switch it into necrosis

Nitric oxide (NO) and its related molecules are important messengers that p lay central roles in pathophysiology. Redox modulation of thiol groups on p rotein cysteine residues by S-nitrosylation can modulate protein function. NO has emerged as a potent regulator of apoptosis in many cell types, eithe r preventing cell death or driving an apoptotic response into a necrotic on e. NO protects neuroblastoma cells from retinoid- and cisplatin-induced apo ptosis, without significantly increasing necrotic cell damage. Nitrosylatio n of thiol groups of several critical factors may be important for cell sur vival. Indeed, S-nitrosylation of the active-site cysteine residue of apopt otic molecules, such as caspases and tissue transglutaminase, results in th e inhibition of their catalytic activities and has important implications f or the regulation of apoptosis by NO. On the other hand, NO is able to shif t the anti-CD95- and ceramide-triggered apoptotic response of Jurkat T cell s into necrotic cell death, in these apoptotic models, NO is therefore unab le to solely inhibit cell death, indicating that it may act below the Feint of no return elicited by CD95-ligation and ceramide stimulation.