Predominant Role of Cytosolic Phospholipase A2α in Dioxin-induced Neonatal Hydronephrosis in Mice

Yoshioka, Wataru; Kawaguchi, Tatsuya; Fujisawa, Nozomi; Aida-Yasuoka, Keiko; Shimizu, Takao; Matsumura, Fumio; Tohyama, Chiharu

doi:10.1038/srep04042

Cited by 11 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Elevated cellular Ca 2+ levels activate Ca 2+ /calmodulin‐dependent kinases (CaMK), which, in turn, may modulate nuclear translocation of the AHR (red arrow in Figure ) (Monteiro et al., ; Gilot et al., ). The in vivo relevance of these findings has been shown for body weight loss and developmental hydronephrosis in mice (Yoshioka et al., ; Fujisawa et al., ). Other examples of alternative pathways include the AHR‐mediated repressed expression of acute‐phase proteins such as serum amyloid A 3 in mouse hepatocytes (9. in Figure ) (Patel et al., ) and functioning of the AHR as a nuclear E3 ubiquitin ligase.…”

Section: Assessmentmentioning

confidence: 72%

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

Knutsen¹,

Alexander²,

Barregård³

et al. 2018

EFS2

143

View full text Add to dashboard Cite

The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of dioxins (PCDD/Fs) and DL‐PCBs in feed and food. The data from experimental animal and epidemiological studies were reviewed and it was decided to base the human risk assessment on effects observed in humans and to use animal data as supportive evidence. The critical effect was on semen quality, following pre‐ and postnatal exposure. The critical study showed a NOAEL of 7.0 pg WHO2005‐TEQ/g fat in blood sampled at age 9 years based on PCDD/F‐TEQs. No association was observed when including DL‐PCB‐TEQs. Using toxicokinetic modelling and taking into account the exposure from breastfeeding and a twofold higher intake during childhood, it was estimated that daily exposure in adolescents and adults should be below 0.25 pg TEQ/kg bw/day. The CONTAM Panel established a TWI of 2 pg TEQ/kg bw/week. With occurrence and consumption data from European countries, the mean and P95 intake of total TEQ by Adolescents, Adults, Elderly and Very Elderly varied between, respectively, 2.1 to 10.5, and 5.3 to 30.4 pg TEQ/kg bw/week, implying a considerable exceedance of the TWI. Toddlers and Other Children showed a higher exposure than older age groups, but this was accounted for when deriving the TWI. Exposure to PCDD/F‐TEQ only was on average 2.4‐ and 2.7‐fold lower for mean and P95 exposure than for total TEQ. PCDD/Fs and DL‐PCBs are transferred to milk and eggs, and accumulate in fatty tissues and liver. Transfer rates and bioconcentration factors were identified for various species. The CONTAM Panel was not able to identify reference values in most farm and companion animals with the exception of NOAELs for mink, chicken and some fish species. The estimated exposure from feed for these species does not imply a risk.

show abstract

Section: Assessmentmentioning

confidence: 72%

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

Knutsen¹,

Alexander²,

Barregård³

et al. 2018

EFS2

143

View full text Add to dashboard Cite

show abstract

“…Abnormalities in the nuclear envelope, nuclear pore, and synapses were observed. The authors speculated that this could be due to the role of shown that cPLA 2 ␣ plays a role in mediating the onset of nonobstructive neonatal hydronephrosis, induced in mice by treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin, which increases expression of cPLA 2 ␣ in the kidneys ( 163 ). Results showed that cPLA 2 ␣ KO neonates have reduced incidence and severity of hydronephrosis that correlates with reduced expression of COX-2, mPGES-1, and lower urinary PGE 2 compared with 2,3,7,8-tetrachlorodibenzo-p-dioxintreated WT pups.…”

Section: Reproductionmentioning

confidence: 99%

Cytosolic phospholipase A2: physiological function and role in disease

Leslie

2015

Journal of Lipid Research

350

257

View full text Add to dashboard Cite

“…The role of AQP2 in the onset of hydronephrosis is not clear because there are some inconsistent observations on the abundance of AQP2 and its localization in the different experiments, such as pharmacological inhibition of V2R (5), nonsense mutation of V2R (58), and our present ( Fig. 4) and previous studies (2,35,55). Studies on short-term regulation and long-term adaptation of apical-trafficking, endocytosis, and expression of AQP2 may elucidate the underlying mechanism.…”

Section: F757mentioning

confidence: 52%

“…Endogenous factors downstream of AhR are believed to modulate a variety of toxic effects, but the mechanism of pathogenesis is not clear (56). Among these, genes encoding enzymes for the production of prostaglandins are responsible for the onset of TCDD-induced neonatal hydronephrosis in mice (35,53,55). AhR-dependent upregulation of cyclooxygenase-2 (COX-2) (10, 35) was shown to play a critical role in the onset of this disease, and the role this was confirmed by the abrogation of TCDD-induced hydronephrosis by treatment with a COX-2-selective inhibitor (35).…”

mentioning

confidence: 99%

Polyuria-associated hydronephrosis induced by xenobiotic chemical exposure in mice

Yoshioka

Kawaguchi

Nishimura

et al. 2016

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

Hydronephrosis is a commonly found disease state characterized by the dilation of renal calices and pelvis, resulting in the loss of kidney function in the severest cases. A generally accepted etiology of hydronephrosis involves the obstruction of urine flow along the urinary tract. In the recent years, we have developed a mouse model of hydronephrosis induced by lactational exposure to dioxin and demonstrated a lack of anatomical obstruction in this model. We also showed that prostaglandin E synthesis system plays a critical role in the onset of hydronephrosis. In the present study, we found that neonatal hydronephrosis was not likely to be associated with functional obstruction (impaired peristalsis) but was found to be associated with polyuria and low urine osmolality with the downregulation of proteins involved in the urine concentrating process. The administration of an antidiuretic hormone analog to the dioxin-exposed pups not only suppressed the increased urine output but also decreased the incidence and severity of hydronephrosis. In contrast to the case in pups, administration of dioxin to adult mice failed to induce polyuria and upregulation of prostaglandin E synthesis system, and the adult mice were resistant to develop hydronephrosis. These findings suggest the possibility that polyuria could induce hydronephrosis in the absence of anatomical or functional obstruction of the ureter. It is concluded that the present animal model provides a unique example of polyuria-associated type of hydronephrosis, suggesting a need to redefine this disease state.

show abstract

Predominant Role of Cytosolic Phospholipase A2α in Dioxin-induced Neonatal Hydronephrosis in Mice

Cited by 11 publications

References 35 publications

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

Cytosolic phospholipase A2: physiological function and role in disease

Polyuria-associated hydronephrosis induced by xenobiotic chemical exposure in mice

Contact Info

Product

Resources

About