Role of PI3K-Akt and MAPK Signaling in Uranyl Nitrate-Induced Nephrotoxicity.

Uranium is a heavy metal of considerable environmental and occupational concern. It is well-known that the kidney is the major target organ of uranium exposure. Elucidating the mechanistic basis of uranium interactions is essential for monitoring the health risk. In the present study, we investigated the cellular mechanisms involved in uranyl nitrate-induced nephrotoxicity. Male Swiss albino mice were administrated with a single intraperitoneal dose of 2 and 4 mg/kg of uranyl nitrate at different time points 1, 3, 5, 7, 14, and 28 days. Uranyl nitrate intoxication-induced apoptosis in the kidney tissue was observed by TUNEL assay. To assess the proliferation, immunohistochemistry was performed using Ki67 proliferative marker followed by western blotting to confirm the involvement of key signaling molecules. The number of TUNEL positive nuclei peaked at third day after uranyl nitrate insult. The increased expression of proliferation marker Ki67 suggests the enhanced DNA repair process prominently at seventh day. Uranyl nitrate administration also resulted in activation of extracellular signal-regulated kinases (ERK), Akt, and c-Jun N-terminal kinases (JNK) expression. All these changes were found to be time-dependent. The result of the current study suggests that uranyl nitrate induces acute renal injury by activation of apoptosis through JNK pathway, while the early activation of signaling molecules Akt and ERK promotes the tubular cell proliferation and cell survival.

Sulfated exopolysaccharide produced by Labrenzia sp. PRIM-30, characterization and prospective applications.

Exopolysaccharides (EPS) are biopolymers produced by bacteria, having potential industrial applications. An EPS produced by a bacterium designated as PRIM-30 isolated from the deep seawater collected from offshore region of Cochin, India was studied. The isolate was identified as Labrenzia sp. based on 16S rRNA gene sequencing. Under optimum conditions for EPS production, the EPS yield was 840mgL(-1) culture medium. The average molecular weight of the EPS was 269kDa and composed of glucose, arabinose, galacturonic acid and mannose in the ratio 14.4:1.2:1:0.6. Importantly, the purified EPS contained 4.76% (w/w) sulfate groups. Viscosity of the (1% w/v) EPS was 3.92cP (shear rate 300s(-1), 25°C). Anodic peak potential (Epa) of the EPS by cyclic voltametric measurement was -0.7V. The EPS showed antioxidant activities with IC50 values of 640 and 190µgmL(-1), respectively, for the inhibition of DPPH and superoxide radicals. The EPS displayed a linear dose dependent increase in total antioxidant capacity and ferric reducing power activities. To date, only a very few marine alphaproteobacterial representatives have been reported for EPS production and this study for the first time, shows the production of a sulfated EPS by a member of the genus Labrenzia.