A03-3

A03-3:Regulation of physiological renal functions via dynamic cellular transports of biometals
Hitomi Fujishiro
(Faculty of Pharmaceutical Sciences, Tokushima Bunri University)
Lab website

Regulation of the body storage of biometals is controlled by the balance of absorption from the gastrointestinal tract and excretion in urine and feces. Urinary excretion of biometals is further regulated by the glomerular filtration and tubular reabsorption. The most important part for renal handling of biometals is the proximal tubules, where a variety of biometal transport systems exist on the apical or basolateral membranes in each segment of the tubules. Therefore, elucidation of the versatile transport systems of biometals in each segment of proximal tubule is critical for understanding the regulations of renal handling of biometals. On the other hand, the kidney frequently becomes a target organ of toxic metals and metal-containing drugs, and dysfunctions of the proximal tubule affect systemic pharmacokinetics of toxic and essential biometals. The purpose of this study is to clarify the transport regulatory mechanisms of biometals and toxic metals using both in vivo and in vitro analysis.We use segment-specific cultured renal cells (in vitro) and the element imaging technology of mouse kidney (in vivo). Finally, we aim to elucidate the dynamics and the homeostasis regulation mechanism of biometals from the studies of both toxic metals and biometals. 

Major publications
*H. Fujishiro, S. Hamao, M. Isawa, and S. Himeno
“Segment-specific and direction-dependent transport of cadmium and manganese in immortalized S1, S2, and S3 cells derived from mouse kidney proximal tubules”
Journal of Toxicological Sciences, 2019 (in press)

*H. Fujishiro and S. Himeno
“New insights of the roles of ZIP8, a cadmium and manganese transporter, and its relation to human diseases”
Biological and Phamaceutical Bulletin, 2019, 42, 1070-1075
doi: 10.1248/bpb.b18-00637

H. Fujishiro, Y. Liu, B. Ahmadi, and *D. M. Templeton
“Protective effect of cadmium-induced autophagy in rat renal mesangial cells”
Archives of Toxicology, 2018, 92, 619-631
doi: 10.1007/s00204-017-2103-x

H. Fujishiro, Y. Yano, Y. Takada, M. Tanihara, and *S. Himeno
“Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells”
Metallomics, 2012, 4, 700-708
doi: 10.1039/c2mt20024d

H. Fujishiro, S. Okugaki, S. Yasumitsu, S. Enomoto, and S. Himeno
“Involvement of DNA hypermethylation in down-regulation of the zinc transporter ZIP8 in cadmium-resistant metallothionein-null cells”
Toxicol. Appl. Pharmacol. 2009, 241, 195-201
doi: 10.1016/j.taap.2009.08.015