[Corrigendum] Nobiletin, a citrus flavonoid, activates vasodilator-stimulated phosphoprotein in human platelets through non­cyclic nucleotide­related mechanisms.

Following the publication of the above paper, the authors noted that the first author affiliation was presented incorrectly. Essentially, 'School of Medicine' had been omitted from the address. Therefore, the author and affiliation details for this paper should have been presented as follows (the changes are highlighted in bold): THANASEKARAN JAYAKUMAR1*, KAO­CHANG LIN1,2*, WAN-JUNG LU1,3, CHIA­YING LIN4, GERALDINE PITCHAIRAJ5, JIUN­YI LI4,6 and JOEN­RONG SHEU1,4. 1Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei; 2Department of Neurology, Chi Mei Medical Center, Tainan; 3Department of Medical Research, Taipei Medical University Hospital; 4Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.; 5Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India; Department of Cardiovascular Surgery, Mackay Memorial Hospital, and Mackay Medical College, Taipei, Taiwan, R.O.C. The authors regret that the error with the first author affiliation was not noticed prior to the publication of their paper, and apologize for any inconvenience caused. [The original article was published in International Journal of Molecular Medicine 39: 174­182, 2017; DOI: 10.3892/ijmm.2016.2822].

Differential intracellular localization of Hsp70 in the gill and heart tissue of fresh water prawn Macrobrachium malcolmsonii during thermal stress.

Exposure of organisms to heat stress induces the expression of evolutionarily conserved proteins called the stress proteins or heat shock proteins (HSPs). At the cellular level, HSPs by acting as molecular chaperone prevents the heat induced aggregation of denatured proteins and play a significant role in adaptation to temperature. Among different HSP family members, Hsp70 is the highly conserved and ubiquitously expressed protein. The present study is carried out to detect changes in the localization of Hsp70/Hsc70 in gill and heart tissues of control and heat shocked juveniles of Macrobrachium malcolmsonii that could be correlated with the functional significance of these two isoforms. Two groups of prawn acclimated at 30 °C were exposed to reported optimum Hsp70 induction temperatures of 36 °C and 38 °C for heart and gill, respectively, for a duration of 48 h. These tissues were processed by immunocytochemical methods to detect intra-cellular localization of Hsp70/Hsc70. Western blotting analysis was performed to determine the cytoplasmic or nuclear localization of Hsp70/Hsc70 and band intensity was detected in total lysate, cytosolic and nuclear extracts of gill and heart tissue. The present investigation clearly shows that there are alterations in the intracellular localization of Hsp70/Hsc70 in the cells of the gill and heart tissues of M. malcolmsonii following heat stress. The western blotting results corroborate the results obtained by immunohistochemical localisation. The differential intracellular localization of Hsp70/Hsc70 appears to indicate the functional roles of this stress protein during exposure to thermal stress.

Nobiletin, a citrus flavonoid, activates vasodilator-stimulated phosphoprotein in human platelets through non-cyclic nucleotide-related mechanisms.

Nobiletin, a bioactive polymethoxylated flavone, has been described to possess a diversity of biological effects through its antioxidant and anti-inflammatory properties. Vasodilator-stimulated phosphoprotein (VASP) is a common substrate for cyclic AMP and cyclic GMP-regulated protein kinases [i.e., cyclic AMP-dependent protein kinase (PKA; also known as protein kinase A) and cyclic GMP-dependent protein kinase (PKG; also known as protein kinase G)] and it has been shown to be directly phosphorylated by protein kinase C (PKC). In the present study, we demonstrate that VASP is phosphorylated by nobiletin in human platelets via a non-cyclic nucleotide-related mechanism. This was confirmed by the use of inhibitors of adenylate cyclase (SQ22536) and guanylate cyclase [1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ)], since they prevented VASP phosphorylation induced by nobiletin. Furthormore, this event was also not affected by specific inhibitors of PKA (H-89), PKG (KT5823) and PKC (Ro318220), representing cyclic nucleotide-dependent pathways upon nobiletin-induced VASP phosphorylation. Similarly, inhibitors of p38 mitogen-activated protein kinase (MAPK; SB203580), extracellular signal-regulated kinase 2 (ERK2; PD98059), c-Jun N-terminal kinase 1 (JNK1; SP600125), Akt (LY294002) and nuclear factor-κB (NF-κB; Bay11-7082) did not affect nobiletin­induced VASP phosphorylation. Moreover, electron spin resonance, dichlorofluorescein fluorescence and western blotting techniques revealed that nobiletin did not affect hydroxyl radicals (OH•), intracellular reactive oxygen species (ROS) and on protein carbonylation, respectively. Furthermore, the nobiletin­induced VASP phosphorylation was surprisingly reversed by the intracellular antioxidant, N-acetylcysteine (NAC), but not by the inhibitor of NADPH oxidase, diphenyleneiodonium chloride (DPI). It was surprising to observe the differential effects of nobiletin and NAC on VASP phosphorylation in human platelets, since they both have been reported to have antioxidant properties. The likely explanation for this discrepancy is that NAC may bind to allosteric sites on the receptor different from those that nobiletin binds to in human platelets. Taken together, our findings suggest that nobiletin induces VASP phosphorylation in human platelets through non-cyclic nucleotide-related mechanisms. Nevertheless, the exact mechanisms responsible for these effects need to be further confirmed in future studies.