Skeletal muscle toxicity biomarkers

Gupta, Ramesh C.; Lasher, Michelle A.; Doss, Robin B.; Milatović, Dejan

doi:10.1016/b978-0-12-404630-6.00017-8

Cited by 12 publications

(8 citation statements)

References 93 publications

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“…This functional enzyme exists as a non‐covalently linked homodimer in the cytosol and consists of two subunits, the brain‐ (B‐type) and muscle‐ (M‐type) type 33 . The concentrations of the resulting three isoenzymes CK‐MM, CK‐BB, and CK‐MB differ in tissues 34–37 . CK‐MM is mainly expressed in skeletal muscle, CK‐MB in heart muscle (myocardium), CK‐BB in brain, smooth muscle, and other energy requiring epithelia, for example, in keratinocytes of the epidermis contributing to the ATP supply during wound healing 38,39 …”

Section: Resultsmentioning

confidence: 99%

“… 14–16 This alkylated peptide might be considered as a novel biomarker for SM poisoning. However, its applicability will be limited due to the various CK concentrations found in different tissues 34,39 and in human blood (CK‐MB concentration range of 18–139 ng/mL 48 ). Exemplarily, the expression of CK is upregulated during wound healing 38 .…”

Section: Resultsmentioning

confidence: 99%

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Identification of creatine kinase and alpha‐1 antitrypsin as protein targets of alkylation by sulfur mustard

Lüling

Schmeißer²,

Siegert

et al. 2020

Drug Testing and Analysis

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Sulfur mustard (SM) is a toxic chemical warfare agent deployed in several conflicts within the last 100 years and still represents a threat in terroristic attacks and warfare. SM research focuses on understanding the pathophysiology of SM and identifying novel biomarkers of exposure. SM is known to alkylate nucleophilic moieties of endogenous proteins, for example, free thiol groups of cysteine residues. The two‐dimensional‐thiol‐differences in gel electrophoresis (2D‐thiol‐DIGE) technique is an initial proteomics approach to detect proteins with free cysteine residues. These amino acids are selectively labeled with infrared‐maleimide dyes visualized after GE. Cysteine residues derivatized by alkylating agents are no longer accessible for the maleimide–thiol coupling resulting in the loss of the fluorescent signal of the corresponding protein. To prove the applicability of 2D‐thiol‐DIGE, this technology was exemplarily applied to neat human serum albumin treated with SM, to lysates from human cell culture exposed to SM as well as to human plasma exposed to CEES (chloroethyl ethyl sulfide, an SM analogue). Exemplarily, the most prominent proteins modified by SM were identified by matrix‐assisted laser desorption/ionization time‐of‐flight (tandem) mass spectrometry, MALDI‐TOF MS(/MS), as creatine kinase (CK) from human cells and as alpha‐1 antitrypsin (A1AT) from plasma samples. Peptides containing the residue Cys282 of CK and Cys232 of A1AT were unambiguously identified by micro liquid chromatography‐electrospray ionization high‐resolution tandem‐mass spectrometry (μLC‐ESI MS/HR MS) as being alkylated by SM bearing the specific hydroxyethylthioethyl‐(HETE)‐moiety. Both peptides might represent potential biomarkers of SM exposure. This is the first report introducing these endogenous proteins as targets of SM alkylation.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Identification of creatine kinase and alpha‐1 antitrypsin as protein targets of alkylation by sulfur mustard

Lüling

Schmeißer²,

Siegert

et al. 2020

Drug Testing and Analysis

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“…Among various cell types for toxicity studies, monocyte cells, the frontline immune cells, were widely used (Gupta, 2014). Monocyte cells are normally derived from bone marrow stem cells and circulated in the bloodstream (Auffray et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

The responses of immune cells to iron oxide nanoparticles

Sherwood

Lackey

et al. 2016

J of Applied Toxicology

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Immune cells play an important role in recognizing and removing foreign objects, such as nanoparticles. Among various parameters, surface coatings of nanoparticles are the first contact with biological system, which critically affect nanoparticle interactions. Here, surface coating effects on nanoparticle cellular uptake, toxicity and ability to trigger immune response were evaluated on a human monocyte cell line using iron oxide nanoparticles. The cells were treated with nanoparticles of three types of coatings (negatively charged polyacrylic acid, positively charged polyethylenimine and neutral polyethylene glycol). The cells were treated at various nanoparticle concentrations (5, 10, 20, 30, 50 μg ml À1 or 2, 4, 8, 12, 20 μg cm À2 ) with 6 h incubation or treated at a nanoparticle concentration of 50 μg ml À1 (20 μg cm À2 ) at different incubation times (6, 12, 24, 48 or 72 h). Cell viability over 80% was observed for all nanoparticle treatment experiments, regardless of surface coatings, nanoparticle concentrations and incubation times. The much lower cell viability for cells treated with free ligands (e.g.~10% for polyethylenimine) suggested that the surface coatings were tightly attached to the nanoparticle surfaces. The immune responses of cells to nanoparticles were evaluated by quantifying the expression of toll-like receptor 2 and tumor necrosis factor-α. The expression of tumor necrosis factor-α and toll-like receptor 2 were not significant in any case of the surface coatings, nanoparticle concentrations and incubation times. These results provide useful information to select nanoparticle surface coatings for biological and biomedical applications.

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“…Tobacco and other substances may similarly modify these relationships (Gupta et al, 2019;Kok et al, 2012). However, examination of the potential impact of substance use on relationships between body composition and frailty among PLWH has not been examined.…”

Section: Introductionmentioning

confidence: 99%

“…Alcohol has multifactorial negative impacts on skeletal muscle health including in PLWH (Molina et al, 2018); such alterations in skeletal muscle may modify the relationship between body composition and frailty. Tobacco and other substances may similarly modify these relationships (Gupta et al, 2019; Kok et al, 2012). However, examination of the potential impact of substance use on relationships between body composition and frailty among PLWH has not been examined.…”

Section: Introductionmentioning

confidence: 99%

Alcohol use, physical activity, and muscle strength moderate the relationship between body composition and frailty risk among people living with HIV

Levitt

Simon

Lin

et al. 2022

Alcoholism Clin & Exp Res

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Background Antiretroviral therapy has improved life expectancy among people living with HIV (PLWH). Despite increased longevity, PLWH are at increased risk of age‐related comorbidities, including frailty. We examined the relationship between body composition and frailty among PLWH, and moderation of this relationship by substance use, physical activity (PA), and physical function. Methods Participants (n = 341; 71% male, 48 ± 10 years, body mass index (BMI) = 27.3 ± 7.0 kg/m2) enrolled in the New Orleans Alcohol Use in HIV (NOAH) study underwent measures of body composition, muscle strength, and gait speed. Whole blood phosphatidylethanol (PEth) was measured, and substance use and PA were self‐reported. Frailty risk measures included the 58‐Item Deficit Index (DI58) and the Veterans Aging Cohort Study (VACS) Index 1.0, where higher scores indicate greater frailty risk. Results Multivariable linear regression adjusted for age, sex, and race showed that higher fat‐free mass index (FFMI), body fat (%), waist‐to‐hip ratio, and body mass index (BMI) ≥ 25.0 kg/m2 vs. < 25.0 kg/m2 were significantly (p < 0.05) associated with decreased frailty risk measured by the VACS Index, whereas adjusted analyses showed no association between body composition variables and the DI58 score. Recent alcohol use, muscle strength, and PA, but not lifetime alcohol use or gait speed, significantly moderated associations between body composition variables and frailty risk with medium‐to‐large effect sizes. Subgroup analyses revealed a negative relationship between DI58 and FFMI among people with PEth > 8 ng/ml and negative relationships of VACS Index with FFMI and WHR in people with lower muscle strength. Overweight or obese BMI categories were positively associated with DI58 in people with lower muscle strength or higher PA level but negatively associated in those with higher muscle strength. Conclusions Our findings indicate that body composition has significant modulatory effects on frailty risk in PLWH, where obesity increases the risk of frailty and greater muscle mass may be protective, even in individuals who use alcohol. These results highlight the importance of considering body composition, physical activity, and physical function in assessing frailty risk in PLWH, particularly among individuals who use alcohol. Moreover, they support the implementation of physical activity interventions to ameliorate the risk of frailty in aging PLWH.

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Skeletal muscle toxicity biomarkers

Cited by 12 publications

References 93 publications

Identification of creatine kinase and alpha‐1 antitrypsin as protein targets of alkylation by sulfur mustard

Identification of creatine kinase and alpha‐1 antitrypsin as protein targets of alkylation by sulfur mustard

The responses of immune cells to iron oxide nanoparticles

Alcohol use, physical activity, and muscle strength moderate the relationship between body composition and frailty risk among people living with HIV

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