Biomedical subjects

Hong-Yan Luo

Publications and source records attributed to Hong-Yan Luo.

7 recordsLinked to original sources

PubMed2024

Nanopore-based full-length transcriptome sequencing for understanding the underlying molecular mechanisms of rapid and slow progression of diabetes nephropathy.

BACKGROUND: Diabetic nephropathy (DN) has been a major factor in the outbreak of end-stage renal disease for decades. As the underlying mechanisms of DN development remains unclear, there is no ideal methods for the diagnosis and therapy. OBJECTIVE: We aimed to explore the key genes and pathways that affect the rate progression of DN. METHODS: Nanopore-based full-length transcriptome sequencing was performed with serum samples from DN patients with slow progression (DNSP, n = 5) and rapid progression (DNRP, n = 6). RESULTS: Here, transcriptome proclaimed 22,682 novel transcripts and obtained 45,808 simple sequence repeats, 1,815 transcription factors, 5,993 complete open reading frames, and 1,050 novel lncRNA from the novel transcripts. Moreover, a total of 341 differentially expressed transcripts (DETs) and 456 differentially expressed genes (DEGs) between the DNSP and DNRP groups were identified. Functional analyses showed that DETs mainly involved in ferroptosis-related pathways such as oxidative phosphorylation, iron ion binding, and mitophagy. Moreover, Functional analyses revealed that DEGs mainly involved in oxidative phosphorylation, lipid metabolism, ferroptosis, autophagy/mitophagy, apoptosis/necroptosis pathway. CONCLUSION: Collectively, our study provided a full-length transcriptome data source for the future DN research, and facilitate a deeper understanding of the molecular mechanisms underlying the differences in fast and slow progression of DN.

Humans↗

PubMed2006

Effect of hypoxia on hyperpolarization-activated current in mouse dorsal root ganglion neurons.

The properties of hyperpolarization-activated current (I(h)) in mouse dorsal root ganglion (DRG) neurons and the effect of hypoxia on the current have been studied using whole-cell configuration of the patch clamp technique. Under voltage-clamp mode, I(h), blocked by 1 mM extracellular CsCl, was present in 75.5% of mouse DRG neurons. The distribution rate increased as the neurons become larger, 5.3%, 79.8% and 94.2% in small, medium and large neurons, respectively. Both I(h) density and the rate of I(h) activation increased in response to more hyperpolarized potential. The activation of I(h) current in larger neuron was faster than in smaller neuron, there was a significant correlation between the time constant of I(h) activation and neuron's size. However, I(h) density did not show any correlation with neuron's size. Under current-clamp mode, 'depolarizing sag' was observed in all neurons with I(h) current. The reversal potential (V(rev)) and the maximal conductance density of I(h) (G(h.max-density)) were -31.0 +/- 4.8 mV and 0.17 +/- 0.02 nS/pF, with a half-activated potential (V(0.5) = -99.4 +/- 1.1 mV) and a slope factor (kappa = -10.2 +/- 0.3 mV). There was a correlation between neuron's size and G(h.max-density) only. According to the effect of hypoxia on resting membrane potential, there were hypoxia-sensitive and hypoxia-insensitive neurons. In the hypoxia-sensitive neurons, I(h) was fully abolished by hypoxia, although the resting membrane potential was hyperpolarized. V(0.5) and V(rev) were shifted about 30 mV toward hyperpolarization, whereas G(h.max-density) and kappa were not affected by hypoxia. We suggest that the kinetics and voltage-dependent characteristics of I(h) are varied in mouse DRG neurons with different size. Hypoxia inhibits I(h) in the hypoxia-sensitive neurons by shifting its activation potential to a more hyperpolarized level.

Animals↗

PubMed2005

Different signal molecules involved in the muscarinic modulation of pacemaker current I(f) on the heart of mouse embryo in different developmental stages.

We isolated mouse embryonic cardiomyocytes derived from timed-pregnant females at different periods and used patch-clamp technique to investigate the muscarinic cholinergic modulation of pacemaker current I(f) in different developmental stages. In early development stage (EDS), muscarinic agonist carbachol (CCh) significantly decreased the magnitude of the pacemaker current I(f) but had no effect in late development stage (LDS). Forskolin (a direct adenylate cyclase activator) and IBMX (a non-selective phosphodiesterase inhibitor) increased I(f) in both EDS and LDS cells. Interestingly, although both forskolin and IBMX increased basal I(f), their effects on CCh-inhibited I(f) were different. Forskolin did not reverse the inhibitory action of CCh until intermediate development stage (IDS). In contrast, IBMX reversed the inhibitory action of CCh on I(f) in EDS but not in IDS. It is suggested that a decrease in intracellular cAMP is a possible mechanism for CCh to modulate I(f). During the EDS and IDS CCh controls the cytoplasmic cAMP level by different pathways: In EDS, CCh modulates I(f) possibly by activating PDE which accelerates the breakdown of cAMP, but in IDS possibly by inhibiting adenylate cyclase (AC) which then reduces the synthesis of cAMP.

Animals↗

PubMed2004

[Chronic intermittent hypoxia decreases acute hypoxic inhibition of voltage-gated potassium channel in rat pulmonary arterial smooth muscle cells].

For determination the ionic mechanisms of the hypoxic acclimatization at the level of channels, male Spradue-Dawley rats were divided into two groups: control normoxic group and chronic intermittent hypoxic group [O2 concentration: (10 +/-0.5)%, hypoxia 8 h a day]. Using whole cell patch-clamp technique, voltage-gated potassium channel currents (IK(V)) were recorded in freshly isolated pulmonary arterial smooth muscle cells (PASMCs) of rat with acute isolated method. The effect of acute hypoxia on IK(V) of PASMCs from chronic intermittent hypoxia group was investigated to offer some basic data for clarifying the ionic mechanisms of the hypoxic acclimatization. The results showed: (1) In control normoxic group, after acute hypoxia free-Ca(2+) solution, the resting membrane potential (Em) of PASMCs was depolarized significantly from -47.2+/-2.6 mV to -26.7+/-1.2 mV, and the IK(V) of PASMCs was decreased significantly from 153.4+/-9.5 pA/pF to 70.1+/-0.6 pA/pF, the peak current percent inhibition was up to (57.6+/-3.3)% at +60 mV, and current-voltage relationship curve shifted to the right. (2) In chronic intermittent hypoxic group, the IK(V) of PASMCs was decreased significantly by exposure to intermittent hypoxia in a time-dependent manner, appeared to start on day 10 and continued to day 30 (the longest time tested) of hypoxia, and current-voltage relationship curve shifted to the right in a time-dependent manner. (3) Compared with the control normoxic group, the percent IK(V) inhibition by acute hypoxia was significantly attenuated in the chronic intermittent hypoxia group and this inhibition effect declined with time exposure to hypoxia. The results suggest that K(V) inhibition was significantly attenuated by chronic intermittent hypoxia, and this effect may be a critical mechanism of the body hypoxic acclimatization.

Animals↗

PubMed2004

[Isolation and electrophysiological characteristics of embryonic cardiomyocytes in mice].

To explore the electrophysiological characteristics of embryonic cardiomyocytes, single embryonic cardiomyocytes were obtained from mice at different periods by a collegenase B digestion approach, whole cell patch clamp recording technique was used to record I(f) and I(Ca-L), and spontaneous action potential was also recorded. The morphological and spontaneous contractile properties of the isolated cells appeared to be typical embryonic cardiomyocytes when the cells were assessed by phase-contrast microscope. Whole cell recording of isolated cells is easily performed by the whole cell patch clamp technique. Elelctrophysiological properties of I(f) and I(Ca-L) from embryonic cardiomyocytes have been proved to be similar to those from adult pacemaker cells or cardiomyocytes. The established method of isolation is simple, stable, effective and reliable. It allows to obtain as early as 8.5-day embryonic myocytes. The electrophysiological recording of embryonic cardiomyocytes will provide a useful model for exploring the electrophysiological characteristics of embryonic cardiomyocytes and the possible mechanism underlying some heart diseases.

Action Potentials↗

PubMed2004

Effects of platelet activating factor on action potentials and potassium channels in guinea-pig ventricular myocytes.

This study was designed to investigate the effects of platelet activating factor (PAF) on the action potential and potassium currents in guinea-pig ventricular myocytes. Whole cell patch clamp techniques were used. With 5 mmol/L ATP in the pipette electrode(mimic normal condition), 1 micromol/L PAF increased APD(90) from 225.8+/-23.3 to 352.8+/-29.8 ms (n=5, P<0.05), decreased I(K1) and I(K) tail currents from -6.1+/-1.3 to -5.6+/-1.1 nA (n=5, P<0.05) at -120 mV and from 173.5+/-16.7 to 152.1+/-11.5 pA (P<0.05, n=4) at +30 mV, respectively. But PAF had no effect on I(K1) at potentials within the normal range of membrane potentials (between -90 mV and +20 mV). In the contrary, without ATP in the pipette electrode by which I(K.ATP) was activated (mimic ischemic condition), 1 micro mol/L PAF shortened APD(90) from 153+/-24.6 to 88.2+/-19.4 ms (n=5, P<0.01). Incubation of myocytes with 1 micro mol/L glibenclamide, a blocker of I(K.ATP ) could restore prolongation of APD induced by PAF. In conclusion, in guinea-pig ventricular myocytes, with 5 mmol/L ATP in the pipette PAF could prolong APD partly due to the inhibition of I(K); while with 0 mmol/L ATP in the pipette, PAF could induce an activation of I(K.ATP), hence a decrease in APD. It is suggested that PAF may amplify the heterogeneity between ischemic and normal cardiac myocytes during ischemia /reperfusion, which may play a vital role in the pathogenesis of the arrhythmias induced by ischemia /reperfusion.

Action Potentials↗

PubMed2002

Inhibitory effect of adrenomedullin on L-type calcium currents in guinea-pig ventricular myocytes.

The effects of adrenomedullin (ADM) on the L-type calcium currents (I(Ca,L)) and the mechanism of the signal transduction process were studied. Enzymatically isolated guinea-pig ventricular myocytes were used to measure ICa,L with whole-cell patch-clamp techniques. ADM at the concentrations of 1-100 nmol/L decreased ICa,L in a dose-dependent manner (P<0.05). ADM22-52) (100 nmol/L), a specific ADM-receptor antagonist, completely abolished the ADM-induced inhibition of ICa,L. Pretreatment of the cells with H-89 (10 micromol/L), a specific PKA inhibitor, did not attenuate the effects of ADM. Intracellular application of 10 micromol/L PKC19-36), a specific PKC inhibitor, prevented the ADM-induced inhibition of the ICa,L, while the specific PKC activator PMA could mimic the effects of ADM on the ICa,L. PMA (1 micromol/L) decreased the ICa,L by 32.26+/-4.20%(P<0.05). These findings indicate that ADM can inhibit the ICa,L in guinea-pig ventricular myocytes, and the inhibition is mediated by the specific ADM-receptor and an activation of protein kinase C.

Adrenomedullin↗