RESUMO
Regulated cell death (RCD) is an essential process that plays key roles along the plant life cycle. Unlike accidental cell death, which is an uncontrolled biological process, RCD involves integrated signaling cascades and precise molecular-mediated mechanisms that are triggered in response to specific exogenous or endogenous stimuli. Ferroptosis is a cell death pathway characterized by the iron-dependent accumulation of lipid reactive oxygen species. Although first described in animals, ferroptosis in plants shares all the main core mechanisms observed for ferroptosis in other systems. In plants as in animals, oxidant and antioxidant systems outline the process of lipid peroxidation during ferroptosis. In plants, cellular compartments such as mitochondria, chloroplasts and cytosol act cooperatively and coordinately to respond to changing redox environments. This particular context makes plants a unique model to study redox status regulation and cell death. In this review, we focus on our most recent understanding of the regulation of redox state and lipid peroxidation in plants and their role during ferroptosis.
Assuntos
Ferroptose , Animais , Ferro/metabolismo , Peroxidação de Lipídeos , Oxirredução , Espécies Reativas de Oxigênio/metabolismoRESUMO
Inflammasomes are multiprotein complexes with an important role in the innate immune response. Canonical activation of inflammasomes results in caspase-1 activation and maturation of cytokines interleukin-1ß and -18. These cytokines can elicit their effects through receptor activation, both locally within a certain tissue and systemically. Animal models of kidney diseases have shown inflammasome involvement in inflammation, pyroptosis and fibrosis. In particular, the inflammasome component nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) and related canonical mechanisms have been investigated. However, it has become increasingly clear that other inflammasome components are also of importance in kidney disease. Moreover, it is becoming obvious that the range of molecular interaction partners of inflammasome components in kidney diseases is wide. This review provides insights into these current areas of research, with special emphasis on the interaction of inflammasome components and redox signalling, endoplasmic reticulum stress, and mitochondrial function. We present our findings separately for acute kidney injury and chronic kidney disease. As we strictly divided the results into preclinical and clinical data, this review enables comparison of results from those complementary research specialities. However, it also reveals that knowledge gaps exist, especially in clinical acute kidney injury inflammasome research. Furthermore, patient comorbidities and treatments seem important drivers of inflammasome component alterations in human kidney disease.
RESUMO
Thiol groups are crucially involved in signaling/homeostasis through oxidation, reduction, and disulphide exchange. The overall thiol pool is the resultant of several individual pools of small compounds (e.g. cysteine), peptides (e.g. glutathione), and thiol proteins (e.g. thioredoxin (Trx)), which are not in equilibrium and present specific oxidized/reduced ratios. This review addresses mechanisms and implications of circulating plasma thiol/disulphide redox pools, which are involved in several physiologic processes and explored as disease biomarkers. Thiol pools are regulated by mechanisms linked to their intrinsic reactivity against oxidants, concentration of antioxidants, thiol-disulphide exchange rates, and their dynamic release/removal from plasma. Major thiol couples determining plasma redox potential (Eh) are reduced cysteine (CyS)/cystine (the disulphide form of cysteine) (CySS), followed by GSH/disulphide-oxidized glutathione (GSSG). Hydrogen peroxide and hypohalous acids are the main plasma oxidants, while water-soluble and lipid-soluble small molecules are the main antioxidants. The thiol proteome and thiol-oxidoreductases are emerging investigative areas given their specific disease-related responses (e.g. protein disulphide isomerases (PDIs) in thrombosis). Plasma cysteine and glutathione redox couples exhibit pro-oxidant changes directly correlated with ageing/age-related diseases. We further discuss changes in thiol-disulphide redox state in specific groups of diseases: cardiovascular, cancer, and neurodegenerative. These results indicate association with the disease states, although not yet clear-cut to yield specific biomarkers. We also highlight mechanisms whereby thiol pools affect atherosclerosis pathophysiology. Overall, it is unlikely that a single measurement provides global assessment of plasma oxidative stress. Rather, assessment of individual thiol pools and thiol-proteins specific to any given condition has more solid and logical perspective to yield novel relevant information on disease risk and prognosis.