■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis

Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity

https://www.kidney-international.org/article/S0085-2538(15)53367-X/pdf

Autophagy is cytoprotective during cisplatin injury of renal proximal tubular cells

Cisplatin is a highly effective antitumor agent whose clinical application is limited by the inherent nephrotoxicity. The current measures of nephroprotection used in patients receiving cisplatin are not satisfactory, and studies have focused on the investigation of new possible protective strategies. Many pathways involved in cisplatin nephrotoxicity have been delineated and proposed as targets for nephroprotection, and many new potentially protective agents have been reported. The multiple pathways which lead to renal damage and renal cell death have points of convergence and share some common modulators. The most frequent event among all the described pathways is the oxidative stress that acts as both a trigger and a result. The most exploited pathways, the proposed protective strategies, the achievements obtained so far as well as conflicting data are summarized and discussed in this review, providing a general view of the knowledge accumulated with past and recent research on this subject.

Cisplatin-induced nephrotoxicity and targets of nephroprotection: an update

The clinical use of cisplatin (cis-diamminedichloroplatinum II) is highly limited by its nephrotoxicity. The precise mechanisms involved in cisplatin-induced mitochondrial dysfunction in kidney have not been completely clarified. Therefore, we investigated in vivo the effects of cisplatin on mitochondrial bioenergetics, redox state, and oxidative stress as well as the occurrence of cell death by apoptosis in cisplatin-treated rat kidney. Adult male Wistar rats weighing 200–220 g were divided into two groups. The control group (n = 8) was treated only with an intraperitoneal (i.p.) injection of saline solution (1 ml per 100 g body weight), and the cisplatin group (n = 8) was given a single injection of cisplatin (10 mg/kg body weight, i.p.). Animals were sacrificed 72 h after the treatment. The cisplatin group presented acute renal failure characterized by increased plasmatic creatinine and urea levels. Mitochondrial dysfunction was evidenced by the decline in membrane electrochemical potential and the substantial decrease in mitochondrial calcium uptake. The mitochondrial antioxidant defense system was depleted, as shown by decreased GSH and NADPH levels, GSH/GSSG ratio, and increased GSSG level. Moreover, cisplatin induced oxidative damage to mitochondrial lipids, including cardiolipin, and oxidation of mitocondrial proteins, as demonstrated by the significant decrease of sulfhydryl protein concentrations and increased levels of carbonylated proteins. Additionally, aconitase activity, which is essential for mitochondrial function, was also found to be lower in the cisplatin group. Renal cell death via apoptosis was evidenced by the increased caspase-3 activity. Results show the central role of mitochondria and the intensification of apoptosis in cisplatin-induced acute renal failure, highlighting a number of steps that might be targeted to minimize cisplatin-induced nephrotoxicity.

Cisplatin-induced nephrotoxicity is associated with oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria

Differential roles of hydrogen peroxide and hydroxyl radical in cisplatin-induced cell death in renal proximal tubular epithelial cells ☆

Purpose: This study analyzed news titles related to nurses in Korea before and after the Coronavirus disease 2019 (COVID 19) pandemic, and aimed to identify the implications of media reports. Methods: Data from January 2019 to December 2020 were collected from BIGKINDS regarding Korean nurses. Text mining and CONCOR analysis were conducted on the top 30 keywords using TEXTOM and Ucinet 6. Results: From the findings of this study, keywords were related to Taewom and Newborn death in 2019. Additionally, because of COVID-19 and the controversy over the encouragement of President Moon Jae-in, Taewom was included in 2020. Using CONCOR analysis, 6 clusters (characteristics and results of major incidents, the issue related target, Newborn abuse, Taewom, drugs, nursing education) were generated in 2019, and 6 clusters (emergency room, hero, controversy, Taewom, COVID-19, hospital infection) were generated in 2020. Conclusion: Before and after the COVID-19 pandemic, most of the news headlines of nurses consisted of negative keywords, while there were few positive news headlines. In order to improve the image of nurses, it is necessary to continuously analyze media trends and establish strategies accordingly. ©2022 Korean Academy of Nursing Administration.

Su Mi Baek

Papers

Differential roles of hydrogen peroxide and hydroxyl radical in cisplatin-induced cell death in renal proximal tubular epithelial cells ☆

Analysis of Headline News about Nurses Before and After the COVID-19 Pandemic