Expression and immunolocalization of metallothioneins MT1, MT2 and MT3 in rat nephron

Sabolić, Ivan; Škarica, Mario; Ljubojević, Marija; Breljak, Davorka; Herak-Kramberger, Carol M.; Crljen, Vladiana; Ljubešić, Nikola

doi:10.1016/j.jtemb.2017.11.011

Cited by 17 publications

(19 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Notably, MT1 is widely expressed in almost every organ to maintain homeostasis. Therefore, it has been most extensively investigated in recent decades (4,7,10,(13)(14)(15)(16)(17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Metallothionein 1: A New Spotlight on Inflammatory Diseases

Dai

Wang

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

MT1 has been demonstrated to be an essential stress protein in maintaining physiological balance and regulating immune homeostasis. While the immunological involvement of MT1 in central nervous system disorders and cancer has been extensively investigated, mounting evidence suggests that MT1 has a broader role in inflammatory diseases and can shape innate and adaptive immunity. In this review, we will first summarize the biological features of MT1 and the regulators that influence MT1 expression, emphasizing metal, inflammation, and immunosuppressive factors. We will then focus on the immunoregulatory function of MT1 on diverse immune cells and the signaling pathways regulated by MT1. Finally, we will discuss recent advances in our knowledge of the biological role of MT1 in several inflammatory diseases to develop novel therapeutic strategies.

show abstract

Section: Introductionmentioning

confidence: 99%

Metallothionein 1: A New Spotlight on Inflammatory Diseases

Dai

Wang

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Additional evidence for the tubular origin of excreted Cd is provided by demonstrated extrusions of MT into tubular lumens [49], documented correlations of E Cd with renal tissue content of Cd [50][51][52], and direct relationships between E Cd and GFR (number of intact nephrons) [53][54][55]. Experiments in rabbits demonstrated a high tubular maximum for reabsorption of CdMT that would preclude excretion of filtered Cd in the typically intoxicated human [56].…”

Section: Discussionmentioning

confidence: 99%

The Source and Pathophysiologic Significance of Excreted Cadmium

Satarug

Vesey

Ruangyuttikarn

et al. 2019

Toxics

View full text Add to dashboard Cite

In theory, the identification of the source of excreted cadmium (Cd) might elucidate the pathogenesis of Cd-induced chronic kidney disease (CKD). With that possibility in mind, we studied Thai subjects with low, moderate, and high Cd exposure. We measured urine concentrations of Cd, ([Cd]u); N-acetyl-β-d-glucosaminidase, a marker of cellular damage ([NAG]u); and β2-microglobulin, an indicator of reabsorptive dysfunction ([β2MG]u). To relate excretion rates of these substances to existing nephron mass, we normalized the rates to creatinine clearance, an approximation of the glomerular filtration rate (GFR) (ECd/Ccr, ENAG/Ccr, and Eβ2MG/Ccr). To link the loss of intact nephrons to Cd-induced tubular injury, we examined linear and quadratic regressions of estimated GFR (eGFR) on ECd/Ccr, eGFR on ENAG/Ccr, and ENAG/Ccr on ECd/Ccr. Estimated GFR varied inversely with both ratios, and ENAG/Ccr varied directly with ECd/Ccr. Linear and quadratic regressions of Eβ2MG/Ccr on ECd/Ccr and ENAG/Ccr were significant in moderate and high Cd-exposure groups. The association of ENAG/Ccr with ECd/Ccr implies that both ratios depicted cellular damage per surviving nephron. Consequently, we infer that excreted Cd emanated from injured tubular cells, and we attribute the reduction of eGFR to the injury. We suggest that ECd/Ccr, ENAG/Ccr, and eGFR were associated with one another because each parameter was determined by the tubular burden of Cd.

show abstract

“…In an experimental study, however, several species of mixed metal complexes such as Cd 3 Cu 3 ZnMT, Cd 4 CuZn 2 MT and Cd 6 CuMT were formed [39]. Unlike Cd, Pb lacks the propensities to induce cellular expression of MT [41,42], but it has particularly high binding affinity for MT isoform 3 (MT-3) [43], expressed prominently in the distal tubule of the kidney [44,45]. Of interest, MT-3 exhibits higher affinity for Cu than MT-1 and MT-2 [46].…”

Section: Discussionmentioning

confidence: 99%

Gender Differences in Zinc and Copper Excretion in Response to Co-Exposure to Low Environmental Concentrations of Cadmium and Lead

et al. 2020

View full text Add to dashboard Cite

Disruption of the homeostasis of zinc (Zn) and copper (Cu) has been associated with nephrotoxicity of cadmium (Cd). Herein, we report the results of a cross sectional analysis of urinary excretion of Zn, Cu, Cd and lead (Pb) in 392 Thais (mean age 33.6) living in an area of low-level environmental exposure to Cd and Pb, reflected by the respective median Cd and Pb excretion rates of 0.44 and 1.75 μg/g creatinine. Evidence for dysregulation of Zn and Cu homeostasis has emerged together with gender differentiated responses. In men, excretion rates for Zn and Cu were increased concomitantly, and their urinary Zn-to-Cu ratios were maintained. In women, only Cu excretion rose, causing a reduction in urinary Zn-to-Cu ratios. Only in women, urinary Zn-to-Cu ratios were associated with worse kidney function, assessed by estimated glomerular filtration rate (eGFR) (β = −7.76, p = 0.015). Only in men, a positive association was seen between eGFR and body iron stores, reflected by serum ferritin (β = 5.32, p = 0.030). Thus, co-exposure to Cd and Pb may disrupt the homeostasis of Zn and Cu more severely in women than men, while urinary Zn-to-Cu ratios and body iron stores can serve as predictors of an adverse effect of co-exposure to Cd and Pb.

show abstract

Expression and immunolocalization of metallothioneins MT1, MT2 and MT3 in rat nephron

Cited by 17 publications

References 78 publications

Metallothionein 1: A New Spotlight on Inflammatory Diseases

Metallothionein 1: A New Spotlight on Inflammatory Diseases

The Source and Pathophysiologic Significance of Excreted Cadmium

Gender Differences in Zinc and Copper Excretion in Response to Co-Exposure to Low Environmental Concentrations of Cadmium and Lead

Contact Info

Product

Resources

About