Hu Lifang
Email Address
phchl@nus.edu.sg
Organizational Units
PHARMACOLOGY
dept
YONG LOO LIN SCH OF MEDICINE
faculty
9 results
Publication Search Results
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Publication Cyclooxygenase-2 mediates the delayed cardioprotection induced by hydrogen sulfide preconditioning in isolated rat cardiomyocytes(2008) Hu, L.-F.; Pan, T.-T.; Neo, K.L.; Yong, Q.C.; Bian, J.-S.; PHARMACOLOGYPublication Negative regulation of β-adrenergic function by hydrogen sulphide in the rat hearts(2008) Yong, Q.C.; Pan, T.-T.; Hu, L.-F.; Bian, J.-S.; PHARMACOLOGYβ-Adrenoceptor is over-stimulated during myocardial ischemia, in which hydrogen sulphide (H2S) concentration was found to be lowered. The present study attempted to investigate if H2S modulates β-adrenoceptor function and the underlying mechanism. We examined the effect of NaHS (a H2S donor) on myocyte contraction and electrically-induced (EI) intracellular calcium ([Ca2+]i) transients upon β-adrenergic stimulation in rat ventricular myocytes with a video edge tracker method and a spectrofluorometric method using fura-2/AM as a calcium indicator, respectively. We found that isoproterenol (ISO, 10- 9-10- 6 M), a β-adrenoceptor agonist, concentration-dependently increased the twitch amplitude of ventricular myocytes, which was attenuated by NaHS (10- 5-10- 3 M) in a dose-dependent manner. The amplitudes and maximal velocities (± dl/dt) of myocyte twitch and EI-[Ca2+]i transient amplitudes were enhanced by ISO, forskolin (an adenylyl cyclase activator), 8-bromoadenosine-3′,5′-cyclic monophosphate (an activator of protein kinase A) and Bay K-8644 (a selective L-type Ca2+ channel agonist). Administration of NaHS (100 μM) only significantly attenuated the effects of ISO and forskolin. Moreover, NaHS reversed ISO-induced cAMP elevation and forskolin-stimulated adenylyl cyclase activity. In addition, stimulation of β-adrenoceptor by ISO significantly decreased endogenous H2S production in rat ventricular myocytes. In conclusion, H2S may negatively modulate β-adrenoceptor function via inhibiting adenylyl cyclase activity. Impairment of this negative modulation during ischemia may induce cardiac arrhythmias. Our study may provide a novel mechanism for ischemia-induced cardiac injury. © 2008 Elsevier Inc. All rights reserved.Publication Hydrogen sulphide regulates calcium homeostasis in microglial cells(2006) Lee, S.W.; Hu, Y.-S.; Hu, L.-F.; Lu, Q.; Dawe, G.S.; Moore, P.K.; Wong, P.T.-H.; Bian, J.-S.; PHARMACOLOGYPublication Hydrogen sulfide inhibits rotenone-induced apoptosis via preservation of mitochondrial function(2009) Hu, L.-F.; Lu, M.; Wu, Z.-Y.; Wong, W.S.F.; Bian, J.-S.; PHARMACOLOGYPublication Hydrogen sulfide attenuates lipopolysaccharide-induced inflammation by inhibition of p38 mitogen-activated protein kinase in microglia(2007) Hu, L.-F.; Wong, W.S.F.; Moore, P.K.; Bian, J.-S.; PHARMACOLOGYPublication H2S preconditioning-induced PKC activation regulates intracellular calcium handling in rat cardiomyocytes(2008) Pan, T.-T.; Neo, K.L.; Hu, L.-F.; Yong, Q.C.; Bian, J.-S.; PHARMACOLOGYPublication Hydrogen sulfide regulates intracellular pH in rat primary cultured glia cells(2010) Lu, M.; Hu, G.; Choo, C.H.; Hu, L.-F.; Tan, B.H.; Bian, J.-S.; PHARMACOLOGYIntracellular pH (pHi) plays an important role in the regulation of central nervous system function. In the present study, we examined whether hydrogen sulfide (H2S), a recently recognized neuromodulator, regulates pHi in rat primary cultured glia cells. pHi was measured with a fluorescent sensitive dye, BCECF-AM. Activities of Cl-/HCO3- exchanger and Na+/H+ exchanger were examined by assessing their capacities to load or extrude H+ upon NH4Cl pulse load. We found that NaHS, a H2S donor, decreased pHi in a concentration-dependent manner ranging from 10 to 200 μM in the primary cultured microglia. Blockade of the Cl-/HCO3- exchanger with, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) or Na+/H+ exchanger with 5-N-methyl-N-isobutylamiloride (MIA) significantly attenuated the pHi-lowering effect of NaHS. Moreover, NaHS significantly increased the activity of Cl-/HCO3- exchanger but inhibited that of Na+/H+ exchanger. The pH regulatory effect of H2S was also observed in primary cultured astrocytes, but not in SH-SY5Y neuronal cells. In conclusion, we found for the first time that H2S induced intracellular acidification in glia cells via regulation of the activities of Cl-/HCO3- exchanger and Na+/H+ exchanger. The present study may provide new evidence for H2S to serve as a neuromodulator and offer a potential approach for the treatment of neurological diseases. © 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society.Publication Hydrogen sulfide protects neurons against hypoxic injury via stimulation of ATP-sensitive potassium channel/protein kinase C/extracellular signal-regulated kinase/heat shock protein90 pathway(2010) Tay, A.S.; Hu, L.F.; Lu, M.; Wong, P.T.H.; Bian, J.S.; PHARMACOLOGYCerebral hypoxia is one of the main causes of cerebral injury. This study was conducted to investigate the potential protective effect of H2S in in vitro hypoxic models by subjecting SH-SY5Y cells to either oxygen-glucose deprivation or Na2S2O4 (an oxygen scavenger) treatment. We found that treatment with NaHS (an H2S donor, 10-100 μM) 15 min prior to hypoxia increased cell viability in a concentration-dependent manner. Time-course study showed that NaHS was able to exert its protective effect even when added 8 h before or less than 4 h after hypoxia induction. Interestingly, endogenous H2S level was markedly reduced by hypoxia induction. Over-expression of cystathionine-β-synthase prevented hypoxia induced cell apoptosis. Blockade of ATP-sensitive K+ (KATP) channels with glibenclamide and HMR-1098, protein kinase C (PKC) with its three specific inhibitors (chelerythrine, bisindolylmaleide I and calphostin C), extracellular signal-regulated kinase 1/2 (ERK1/2) with PD98059 and heat shock protein 90 (Hsp90) with geldanamycin and radicicol significantly attenuated the protective effects of NaHS. Western blots showed that NaHS significantly stimulated ERK1/2 activation and Hsp90 expression. In conclusion, H2S exerts a protective effect against cerebral hypoxia induced neuronal cell death via KATP/PKC/ERK1/2/Hsp90 pathway. Our findings emphasize the important neuroprotective role of H2S in the brain during cerebral hypoxia. © 2010 IBRO.Publication Hydrogen sulfide protects astrocytes against H2O2-induced neural injury via enhancing glutamate uptake(2008) Lu, M.; Hu, L.-F.; Bian, J.-S.; Hu, G.; PHARMACOLOGYExcess extracellular glutamate, the main excitatory neurotransmitter, may result in excitotoxicity and neural injury. The present study was designed to study the effect of hydrogen sulfide (H2S), a novel neuromodulator, on hydrogen peroxide (H2O2) -induced glutamate uptake impairment and cellular injuries in primary cultured rat cortical astrocytes. We found that NaHS (an H2S donor, 0.1-1000 μM) reversed H2O2-induced cellular injury in a concentration-dependent manner. This effect was attenuated by L-trans-pyrrolidine-2,4-dicarboxylic (PDC), a specific glutamate uptake inhibitor. Moreover, NaHS significantly increased [3H]glutamate transport in astrocytes treated with H2O2, suggesting that H2S may protect astrocytes via enhancing glutamate uptake function. NaHS also reversed H2O2-impaired glutathione (GSH) production. Blockade of glutamate uptake with PDC attenuated this effect, indicating that the effect of H2S on GSH production is secondary to the stimulation of glutamate uptake. In addition, it was also found that H2S may promote glutamate uptake activity via decreasing ROS generation, enhancing ATP production and suppressing ERK1/2 activation. In conclusion, our findings provide direct evidence that H2S has potential therapeutic value for oxidative stress-induced brain damage via a mechanism involving enhancing glutamate uptake function. © 2008 Elsevier Inc. All rights reserved.