Inhibitory effects of 1,25-dihydroxyvitamin D(3) and its low-calcemic analogues on staurosporine-induced apoptosis.
Journal Title: Pharmacological Reports - Year 2007, Vol 59, Issue 4
Abstract
The active form of vitamin D(3) and some of its related compounds show neuroprotective effects in various models of neuronal damage, however, mechanism of their anti-apoptotic action has not been elucidated. Therefore, the present study was designed to investigate the effects of 1,25-dihydroxyvitamin D(3) and its low-calcemic analogues, PRI-2191, PRI-1890 and PRI-1901 on staurosporine-induced apoptosis in human neuroblastoma SH-SY5Y cells. Twenty-four hour incubation with staurosporine (1 muM) enhanced the caspase-3 activity, decreased mitochondrial membrane potential and increased the number of apoptotic cells as visualized by Hoechst staining. 1,25-Dihydroxyvitamin D(3) and PRI-2191 attenuated the staurosporine-induced caspase-3 activity at 5, 50 and 500 nM, whereas PRI-1890 and PRI-1901 were active only at higher concentrations. Furthermore, 1,25-dihydroxyvitamin D(3) (50 and 500 nM) and PRI-2191 (500 but not 50 nM) reversed the staurosporine-evoked decrease in mitochondrial membrane potential. Hoechst and calcein staining confirmed the neuroprotective effects of the secosteroids under study. Further study revealed that a selective inhibitor of phosphatidylinositol 3-kinase (PI3-K), wortmannin, at concentration of 100 nM antagonized the effect of 1,25-dihydroxyvitamin D(3) and PRI-2191 on staurosporine-induced caspase-3 activation. These data indicate that 1,25-dihydroxyvitamin D(3) and its low-calcemic analogues at nanomolar concentrations inhibited mitochondrial pathway of apoptosis in SH-SY5Y neuronal cells, though with different potency. Moreover, the activation of PI3-K/Akt signaling pathway appears to play a role in anti-apoptotic effects of the secosteroids.
Authors and Affiliations
Magdalena Regulska, Monika Leśkiewicz, Bogusława Budziszewska, Andrzej Kutner, Danuta Jantas, Agnieszka Basta-Kaim, Marta Kubera, Lucylla Jaworska-Feil, Władysław Lasoń
Keywords
Related Articles
- EP ID EP133999
- DOI -
- Views 95
- Downloads 0
Antinociceptive effect of lidocaine in rats.
Lidocaine, a local anesthetic drug, exerts its effect by blocking sodium channels in peripheral sensory neurons. It is commonly used in clinical practice as a local anesthetic drug. This study was undertaken in order to...
Concomitant use of tramadol and venlafaxine - evaluation of antidepressant-like activity and other behavioral effects in rats.
The aim of this study was to evaluate antidepressant-like effect (Porsolt test), locomotor activity and motor coordination of joint administration of tramadol (TRM) and venlafaxine (VEN) in rats.
Antiatherogenic effect of quercetin is mediated by proteasome inhibition in the aorta and circulating leukocytes.
Quercetin, a plant-derived flavonoid, has attracted considerable attention as promising compound for heart disease prevention and therapy. It has been linked to decreased mortality from heart disease and decreased incide...
Inhibition of neutral endopeptidase by thiorphan does not modify coronary vascular responses to angiotensin I, angiotensin II and bradykinin in the isolated guinea pig heart.
Both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) are involved in the regulation of renin-angiotensin and kallikrein-kinin systems. The aim of the present study was to assess the role of NEPand ACE...
Circadian time-dependent chemopreventive potential of withaferin-A in 7,12-dimethylbenz[a]anthracene-induced oral carcinogenesis.
Circadian time-dependent treatment with chemotherapeutic drugs (chronotherapy) optimizes the therapeutic index by maximizing treatment efficacy and minimizing toxicity. The circadian time-dependent chemopreventive and an...