Calcium/Calmodulin Mediates Cardiomyocyte Ferroptosis in Myocardial Infarction Through Iron Overload / 中国生物化学与分子生物学报

Myocardial infarction(MI), an acute coronary syndrome that poses a serious risk to human health, involves multiple pathophysiological processes, including calcium overload. Existing therapeutic approaches and preventive measures have limitations and cannot effectively repair myocardial cells with poor regenerative potential. Exploring multiple programmed modes of cardiomyocyte death could help find potential targets for the treatment of myocardial infarction, and the potential role of ferroptosis as a novel mode of cell death in myocardial infarction has attracted great attention. The aim of this study was to investigate whether Ca

Research progress on the role of thrombospondin in synapse formation / 中国修复重建外科杂志

Objective: To review the recent progress in the role of thrombospondins (TSPs) in synapse formation in the central nervous system (CNS). Methods: A wide range of domestic and foreign literature on the role of TSPs in the synapse formation of the CNS was reviewed. The role of TSPs in structural features, molecules, and related diseases was reviewed. Results: As an oligosaccharide protein, TSPs play important roles in angiogenesis, inflammation, osteogenesis, cell proliferation, and apoptosis. In the nervous system, they bind to voltage-dependent calcium channels, neuronectin, and other extracellular matrix proteins and cell surface receptors, and participate in and regulate multiple processes such as synapse formation, maturation, and function in the CNS. Conclusion: TSPs as an oligomeric extracellular matrix protein play an important role in the formation of synapses and the repair of synapses after CNS injury.

Effects of T-type calcium channel inhibitors on monocrotaline-induced pulmonary arterial hypertension in rats / 中华实用儿科临床杂志

Objective To investigate the effects of T-type calcium channel inhibitors (ProTx-1,micromolar Ni2+ and Mibefradil) on Monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats.Methods Forty male Sprague-Dawley rats were randomly divided into 5 groups:normal control group,MCT group,ProTx-1 group,micromolar Ni2+ group and Mibefradil group (8 cases in each group).The right ventricular systolic pressure (RVSP),the right ventricular hypertrophy index (RVHI),and the index of pulmonary vascular remodeling(MA％) were measured on day 28 after MCT-treatment.Western blot was used to detect the expression of proliferating cell nuclear antigen(PCNA) and Cleaved Caspase-3 in pulmonary artery.Results (1)RVSP and RVHI in MCT group were significandy higher than those in the other 4 groups (F =21.55,P ＜ 0.01;F =15.63,P ＜ 0.01).The two indexes in 3 intervention groups were higher than those in normal control group (all P ＜ 0.05),nevertheless,significantly lower than those in MCT group,and 3 intervention groups showed no significant differences (all P ＞ 0.05).(2) MA％ in normal control group [(23.43 ± 1.95) ％] was lower than that in MCT group [(80.42 ± 4.30) ％],ProTx-1 group [(60.35 ± 3.83)％],micromolar Ni2+ group[(62.44 ± 3.81)％] and Mibefradil group[(58.66 ± 4.23)％] (F =216.2,P ＜ 0.01);3 intervention groups showed no significant differences (all P ＞ 0.05),however,they were all significantly lower than that in MCT group.(3) The expression of PCNA in MCT group was higher than that in normal control group,meanwhile,3 intervention groups were significantly lower than that in MCT group.The expression of Cleaved Caspase-3 in MCT group was higher than that in normal control group,nevertheless,3 intervention groups showed no significant changes compared with MCT group,respectively.Conclusions T-type calcium channel inhibitors could ameliorate the progression of MCT-PAH in rats,mainly through suppressing the proliferation of pulmonary artery smooth muscle cells.

Differential regulation of Purkinje cell dendritic spines in rolling mouse Nagoya (tg(rol)/tg(rol)), P/Q type calcium channel (alpha1(A)/Ca(v)2.1) mutant / 대한해부학회지

Voltage dependent calcium channels (VDCC) participate in regulation of neuronal Ca2+. The Rolling mouse Nagoya (Cacna1a(tg-rol) ) is a spontaneous P/Q type VDCC mutant, which has been suggested as an animal model for some human neurological diseases such as autosomal dominant cerebellar ataxia (SCA6), familial hemiplegic migraine and episodic ataxia type-2. Morphology of Purkinje cell (PC) dendritic spine is suggested to be regulated by signal molecules such as Ca2+ and by interactions with afferent inputs. The amplitude of excitatory postsynaptic current was decreased in parallel fiber (PF) to PC synapses, whereas apparently increased in climbing fiber (CF) to PC synapses in rolling mice Nagoya. We have studied synaptic morphology changes in cerebella of this mutant strain. We previously found altered synapses between PF varicosity and PC dendritic spines. To study dendritic spine plasticity of PC in the condition of insufficient P/Q type VDCC function, we used high voltage electron microscopy (HVEM). We measured the density and length of PC dendritic spines at tertiary braches. We observed statistically a significant decrease in spine density as well as shorter spine length in rolling mice compared to wild type mice at tertiary dendritic braches. In proximal PC dendrites, however, there were more numerous dendritic spines in rolling mice Nagoya. The differential regulation of rolling PC spines at tertiary and proximal dendrites in rolling mice Nagoya suggests that two major excitatory afferent systems may be regulated reciprocally in the cerebellum of rolling mouse Nagoya.

Voltage-dependent Calcium Channel (VDCC) alpha(1A) Subunit Expression in the Ataxic Mutant, Pogo Mice Cerebellum / 대한해부학회지

The pogo mouse is a new ataxic mutant derived from a Korean wild mouse. The pogo mutation is inherited as an autosomal recessive trait on chromosome 8. Mutations in gene coding for the alpha(1A)subunit of voltagegated P/Q-type Ca(2+) channel have been shown to cause phenotypes in humans and mice, i.e., tottering, leaner, rolling mouse mouse Nagoya. Using immunohistochemistry, the expression of the alpha(1A)subunit of voltage-gated P/Q-type Ca(2+) channel was examined in pogo mice cerebellum including deep cerebellar nuclei (DCN). We observed alpha(1A)immunoreactivity in the cerebellar cortex (Purkinje cell and granule cell) and DCN of ataxic pogo mice and heterozygote control mice. There was no difference in cerebellar cortical alpha(1A)immunoreactivity between ataxic pogo mice and heterozygous littermate controls (pogo/+). However, we observed alpha(1A)immunoreactivity in the Purkinje cells of control and ataxic pogo mice cerebellum and DCN. We found a significant difference between pogo and heterozygous controls in terms of alpha(1A)immunoreactivities in the DCN. alpha(1A)immunoreactivity in this nucleus in pogo was much higher than in heterozygous littermate controls. No significant differences were observed in the interposed nucleus between pogo and heterozygous controls, but we found that the alpha(1A)subunits were clearer and more abundant in the lateral and medial regions of pogo than in control mice in these regions, where only weak immunoreactivity was observed. This elevated expression of the alpha(1A)subunit in deep cerebellar neurons of pogo might be a compensation for the altered function of P/Q type calcium channel and be related with the induction of the ataxic phenotype in pogo mice.

Effects of resveratrol on isolated coronary artery rings of canine / 中国临床药理学与治疗学

AIM: To investigate the relaxative characteristics of resveratrol(RES) and 17?-Estradiol(EST) on coronary arteries in dogs and its mechanism.METHODS: Rings of canine coronary arteries were suspended in organ baths containing Krebs-Henseleit solution,and then isometric tension was measured.RESULTS: Both RES and EST caused the does-response contractile curve of KCl in K-H solution and CaCl_2 in Ca~(2+)-free K-H solution shift rightward,and their sensitivies and the values of maximum contractions had been decreased.In the N?-L-nitro-arginine,Methylene Blue and Sodium Orthovanadate groups,the vasorelaxant effects of both estrogens were markedly attenuated(P(0.05)).CONCLUSION: Resveratrol and 17?-Estradiol relaxe vascular smooth muscle in an endothelium-dependent manner,and are not related to KATP channel.

The developmental expression of voltage dependent calcium channel alpha1 subunits (alpha1D, alpha1B, alpha1A, alpha1E) mRNA in the rat brain / 대한해부학회지

Voltage dependent calcium channels (VDCCs) mediate Ca++ influx into cells and are responsible for regulation of a variety of physiological effects. The key functional property of VDCCs are attributed to the calcium-pore forming alpha1 subunit. In this study, distribution pattern of alpha1 subunit (alpha1D, alpha1B, alpha1A, alpha1E) mRNA of VDCCs in developing and adult rat brain was investigated by in situ hybridization histochemistry. In the adult rat brain, each alpha1 subunit mRNA displayed a specific and distinct distribution pattern. alpha1D was highly expressed in the olfactory bulb, dentate gyrus, pituitary gland, pineal gland, hypothalamus, superior colliculus and cerebellum. Relatively low level of alpha1B was expressed throughout the whole brain and strong expression of alpha1A was observed in CA3 area of Ammon's horn, medial geniculate body, inferior colliculus and cerebellum. High level of alpha1E was found in the olfactory bulb, hippocampus, dentate gyrus, medial habenular nucleus and cerebellum. Moreover, alpha1B, alpha1A and alpha1E were expressed only in the nervous system but alpha1D was expressed not only in the nervous system but also in other tissues including liver, heart, lung and skeletal muscle. Generally the expression of alpha1D, alpha1A, and alpha1E subunit was observed from E14 and thereafter the intensity of labeling was gradually increased to P14 and then decreased to the adult level. But the expression of alpha1B subunit was observed from E14 and gradually increased to E20 and P0 and then decresaed. From the differential expressions of VDCC alpha1 subunits in developing and adult rat brain, it is suggested that each type of VDCCs may play a distinct roles in neural and nonneural tissues, and the VDCCs may be related with development of nervous system.

Cloning and localization of two forms of voltage-dependent calcium channel beta3 subunit gene / 대한해부학회지

Voltage-dependent calcium channel (VDCC) is composed of at least four subunits: alpha1, alpha2, beta, delta. Four mammalian beta subunit isoforms (beta1, beta2, beta3 and beta4) have been identified from nervous system. beta subunit accelerates the kinetics of activation (channel openning) and inactivation (channel closure), and regulates the channel activity by phosphorylation through various signal transduction mechanisms. We have cloned three cDNAs (RB8, RB10, and RB11) encoding beta3 subunit of voltage-dependent calcium channel from rat cDNA library using the oligonucleotides of which sequences obtained from the highly conserved regions of rat b subunits. The RB8 and RB10 (rtB3a) encode a same protein of 484 amino acids with estimated Mr of 54,571 Da, which was identical to beta3 subunit gene previously reported. The RB11 (rtbBb) is diffferent from RB10 at N-terminal region but shares common amino acid sequences from the glycine, the 16th amino acid of RB10, to the end of the gene. Open reading frame of RB10 encodes a 483 amino-acid protein with a predicted Mr of 54,473 Da. The RB10 and RB11 are suspected to be alternatively spliced variants from a single b3 subunit gene. The existence of the variants was confirmed by RT-PCR using the oligonucleotide primers from the specific sequences of each variant. The expression patterns of VDCC beta3 (rtB3a) and its specific variant (rtB3b) were investigated in the rat brain by in situ hybridization histochemistry. The mRNAs for rtB3a and rtB3b were exclusively expressed in the nervous system. In the brain, strong expression of both mRNAs (rtB3a and rtB3b) was found in the medial habenular nucleus of thalamus, hippocampus, dentate gyrus, olfactory bulb and cerebellum. But significant discrepancy of expression was found in the lateral posterior thalamic nucleus and olfactory bulb. From these results, it is suspected that newly cloned VDCC variant (rtB3b) should be the alternatively spliced variant of VDCC beta3 gene.

Chromosomal Mapping and Brain Distribution of alpha1 Subunit of N-type Voltage Dependent Calcium Channel / 대한해부학회지

Voltage dependent calcium channels mediate wide variety of physiological functions including neurotransmitter release, neurite outgrowth, and gene expression in neurons. omega-Conotoxin-sensitive N-type calcium channels are exclusively expressed in nervous system and involved in the control of neurotransmitter release from neurons. In this experiment, I have investigated human chromosomal location and rat neuronal distribution of N-type voltage dependent calcium channel alpha1, subunit [alpha1B]. I have localized human alpha1B subunit gene to the long arm of chromosome 9[9q34] by fluorescent in situ hybridization. The distribution of rat alphaB1 subunit mRNA has been examined in the rat brain by in situ hybridization histochemistry and high level of alpha1B subunit mRNA has been observed in olfactory bulb, anterior olfactory nucleus, cerebral cortex, piriform cortex, hippocampus, dentate gyrus, parabrachial nucleus, and cerebellum and low level of expression was also found in other areas of rat brain.