Neuronal expression of SGK1 in aged human brain and its nuclear compartmentalization suggest a possible neuroprotective role. FOXO3a and NDRG1 data suggest augmented SGK1 activity (as reported for Akt) in severe AD. Increased intracellular SGK1 may complement enhanced Akt, with a distinct subcellular localization.

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Nephrotoxicity is one of the serious dose-limiting complications of methotrexate (MTX) when used in the treatment of various malignancies and nononcological diseases. The aim of this study was to investigate the role of poly(adenosine diphosphate ribose) polymerase (PARP) activity in MTX-induced nephrotoxicity. Rats were divided into 4 groups as control, MTX treated (MTX, 7 mg/kg per d, intraperitoneally [ip], once daily for 3 consecutive days), MTX plus 1,5-isoquinelinediol (ISO, a PARP inhibitor, 3 mg/kg per d, i.p.) treated, or ISO treated. Histopathology of kidneys was evaluated by light microscopy. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay was used to analyze apoptosis in kidney sections. Blood urea nitrogen (BUN), serum creatinine, and urinary N-acetyl-β-d-glucosaminidase (NAG) were used as biochemical markers of MTX-induced renal injury. Our results showed that MTX administration significantly increased BUN, serum creatinine, and urinary NAG levels. The PARP-1 and PAR (a product of PARP activity) expression and apoptotic cell death were also markedly increased in renal tubules after MTX administration. The ISO treatment attenuated MTX-induced renal injury, as indicated by BUN and serum creatinine levels, urinary NAG excretion, and renal histology. The PARP inhibitor treatment reduced PARP-1 and PAR expression to levels similar to that of controls. These results revealed that ISO may have a protective effect against the nephrotoxic effects of MTX by inhibiting PARP activation. This is the first study that demonstrates the role of PARP activation in MTX-induced nephrotoxicity and tubular apoptosis.

Rapamycin (mTOR inhibitor) has been reported to have negative effect on human male gonadal function. Previously, we showed that mTOR signalling molecules are expressed during early spermatogenesis in mice. The objective of this study was to investigate the role of mTOR signalling in meiosis both during the first wave of spermatogenesis and also during adult spermatogenesis. Day 5 post-partum mice were administered rapamycin and retinoic acid (RA; a Stra8 activator), and expression of p-p70S6K and Stra8 proteins was evaluated. p-p70S6K and Stra8 protein expressions decreased in post-natal testes after rapamycin treatment. Stra8 protein expression increased after RA and rapamycin+RA administrations in post-natal testes. In adult mice, rapamycin was administrated for 1 or 4 weeks. Morphological analysis for testicular damage and TUNEL assay was performed. After rapamycin administration, germ cell loss increased in adult testes. Ultrastructural analysis revealed disorganised testicular morphology and vacuolisation. The number of apoptotic germ cells increased after 4 weeks rapamycin administration. Stra8 and Dmc1 expressions decreased in 4 weeks rapamycin group, whereas Sycp3 and VASA expression did not change. Our findings suggest that mTOR pathway has an important role in meiotic progress of male germ cells both during first wave of spermatogenesis and in adult mice.