Protein S-nitrosylation: Role for nitric oxide signaling in neuronal death

Abstract

One of the signaling mechanisms mediated by nitric oxide (NO) is through S-nitrosylation, the reversible redox-based modification of cysteine residues, on target proteins that regulate a myriad of physiological and pathophysiological processes. In particular, an increasing number of studies have identified important roles for S-nitrosylation in regulating cell death. These roles include double-edged effects dependent on the levels, spatiotemporal distribution, and origins of NO in the brain: in general S-nitrosylation resulting from the basal low level of NO in cells exerts anti-cell death effects, whereas S-nitrosylation elicited by induced NO upon stressed conditions is implicated in either pro-cell death effects or serves as a negative feedback mechanism and inhibits cell death. Furthermore, in addition to these cascades, mainly associated with apoptosis, massive levels of NO can lead to necrotic cell death. This review focuses on the proteins that are regulated by S-nitrosylation during cell death, in particular neuronal cell death and apoptosis. These mechanisms are involved in the pathogenesis of several diseases including degenerative diseases of the central nervous system (CNS).

Increased oxidative stress and oxidative DNA damage in non-remission schizophrenia patients

“…It is shown that oxidative stress cause cell death and apoptosis by activating several intrinsic pathways. (Sen et al, 2008;Shahani and Sawa, 2012). And it is suggested that these processes may implicated in the ethiopathogenesis of several degenerative diseases of the central nervous system (Shahani and Sawa, 2012).…”

“…(Sen et al, 2008;Shahani and Sawa, 2012). And it is suggested that these processes may implicated in the ethiopathogenesis of several degenerative diseases of the central nervous system (Shahani and Sawa, 2012). As far as our knowledge there is not a study which examines the relationship between oxidative DNA damage and oxidative stress in patients with schizophrenia.…”

Role of Apoptosis Signal-regulating Kinase 1 (ASK1) as an Activator of the GAPDH-Siah1 Stress-Signaling Cascade

“…In the nucleus, GAPDH modulates several proteins, in particular stimulating the catalytic activity of acetyltransferase p300/CREB-binding protein (CBP) that regulates transcription of various genes (22). Therefore, GAPDH may modulate homeostatic control by bridging energy supply (glycolytic pathway) to stress response (GAPDHSiah1 cascade), which is finely regulated by post-translational modification (23)(24)(25)(26).…”

Nitric Oxide, Coagulation and Cancer

“…Furthermore, NO ignites the caspase cascade that is responsible for releasing mitochondrial cytochrome C into the cytosol that is ultimately responsible for initiating the chain of apoptotic events [67,79]. NO and its relationship to p53 has proven to be baffling.…”