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Author

Hong Zhang

Other affiliations: Lanzhou University
Bio: Hong Zhang is an academic researcher from Chinese Academy of Sciences. The author has contributed to research in topics: Apoptosis & Oxidative stress. The author has an hindex of 24, co-authored 97 publications receiving 1474 citations. Previous affiliations of Hong Zhang include Lanzhou University.


Papers
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Journal ArticleDOI
TL;DR: It is suggested that starvation-induced endocytosis via NAD+-CD38-cADPR-Ca2+ signaling could be a new mechanism of mitochondrial transplantation to rescue aerobic respiration and attenuate the Warburg effect.
Abstract: Emerging evidence indicates that reprogramming of energy metabolism involving disturbances in energy production from a defect in cellular respiration with a shift to glycolysis is a core hallmark of cancer. Alterations in cancer cell energy metabolism are linked to abnormalities in mitochondrial function. Mitochondrial dysfunction of cancer cells includes increased glycolysis, decreased apoptosis, and resistance to radiotherapy. The study was designed for two main points: firstly, to investigate whether exogenous functional mitochondria can transfer into glioma cells and explore the underlying molecular mechanisms from the perspective of endocytosis; secondly, to further verify whether the mitochondrial transplantation is able to rescue aerobic respiration, attenuate the Warburg effect and enhance the radiosensitivity of gliomas. Methods: Mitochondria were isolated from normal human astrocytes (HA) and immediately co-incubated with starved human glioma cells (U87). Confocal microscopy and gene sequencing were performed to evaluate the ability of isolated mitochondria internalization into U87 cells. The interaction between endocytosis and isolated mitochondria transfer were captured by 3D tomographic microscopy and transmission electron microscopy. NAD+, CD38, cADPR and Ca2+ release were determined by commercial kits, western blot, HLPC-MS and Fluo-3 AM respectively. PCR array expression profiling and Seahorse XF analysis were used to evaluate the effect of mitochondrial transplantation on energy phenotypes of U87 cells. U87 cells and U87 xenografts were both treated with mitochondrial transplantation, radiation, or a combination of mitochondrial transplantation and radiation. Apoptosis in vitro and in vivo were detected by cytochrome C, cleaved caspase 9 and TUNEL staining. Results: We found that mitochondria from HA could be transferred into starved U87 cells by simple co-incubation. Starvation treatment slowed the rate of glycolysis and decreased the transformation of NAD+ to NADH in U87 cells. A large amount of accumulated NAD+ was released into the extracellular space. CD38 is a member of the NAD+ glycohydrolase family that catalyzes the cyclization of extracellular NAD+ to intracellular cADPR. cADPR triggered release of Ca2+ to promote cytoskeleton remodeling and plasma membrane invagination. Thus, endocytosis involving isolated mitochondria internalization was mediated by NAD+-CD38-cADPR-Ca2+ signaling. Mitochondrial transfer enhanced gene and protein expression related to the tricarboxylic acid (TCA) cycle, increased aerobic respiration, attenuated glycolysis, reactivated the mitochondrial apoptotic pathway, inhibited malignant proliferation of U87 cells. Isolated mitochondria injected into U87 xenograft tumors also entered cells, and inhibited glioma growth in nude mice. Mitochondrial transplantation could enhance the radiosensitivity of gliomas in vitro and in vivo. Conclusion: These findings suggested that starvation-induced endocytosis via NAD+-CD38-cADPR-Ca2+ signaling could be a new mechanism of mitochondrial transplantation to rescue aerobic respiration and attenuate the Warburg effect. This mechanism could be a promising approach for radiosensitization.

79 citations

Journal ArticleDOI
TL;DR: A green and sustainable synthetic strategy to combine these procedures into one step and to produce highly luminescent carbon quantum dots (CQDs), which can also be easily fabricated into flexible thin films with intense luminescence for future roll-to-roll manufacturing of optoelectronic devices.
Abstract: Photoluminescent carbon and/or silicon-based nanodots have attracted ever increasing interest. Accordingly, a myriad of synthetic methodologies have been developed to fabricate them, which unfortunately, however, frequently involve relatively tedious steps, such as initial surface passivation and subsequent functionalization. Herein, we describe a green and sustainable synthetic strategy to combine these procedures into one step and to produce highly luminescent carbon quantum dots (CQDs), which can also be easily fabricated into flexible thin films with intense luminescence for future roll-to-roll manufacturing of optoelectronic devices. The as-synthesized CQDs exhibited enhanced cellular permeability and low or even noncytotoxicity for cellular applications, as corroborated by confocal fluorescence imaging of HeLa cells as well as cell viability measurements. Most strikingly, zebrafish were directly fed with CQDs for in vivo imaging, and mortality and morphologic analysis indicated ingestion of the CQDs posed no harm to the living organisms. Hence, the multifunctional CQDs potentially provide a rich pool of tools for optoelectronic and biomedical applications.

77 citations

Journal ArticleDOI
TL;DR: The results suggest that salidroside inhibits tumor cells metastasis, which may due to its interfere in the intracellular excess ROS thereby down-regulated the ROS-PKC-ERK1/2 signaling pathway.

69 citations

Journal ArticleDOI
Yi Xie1, Qiu Yue Zhao1, Hongyan Li1, Xin Zhou1, Yang Liu1, Hong Zhang1 
TL;DR: This study confirmed the antagonistic roles of curcumin to counteract radiation-induced cerebral injury in vivo and suggested that the potent Nrf2 activation capability might be valuable for the protective effects ofCurcumin against radiation.
Abstract: Oxidative stress is one of the major mechanisms implicated in carbon ion irradiation. Curcumin is a natural phenolic compound with impressive antioxidant properties. What's more, curcumin is recently proved to exert its effects partly radioprotection. In vivo, we investigated the protective effects of curcumin against (12)C(6+)radiation-induced cerebral injury. Our results showed that 4Gy heavy ion radiation-induced spatial strategy and memory decline and reduction of brain superoxide dismutase (SOD) activity levels were all consistently improved by curcumin, and the augmentation of cerebral malonaldehyde (MDA) was lowered by curcumin. Furthermore, both the cerebral cells nuclear erythroid 2-related factor 2 (Nrf2) protein and three typically recognized Nrf2 downstream genes, NAD(P)H quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and γ-glutamyl cysteine synthetase (γ-GCS) were consistently up-regulated in curcumin-pretreated mice. Our study confirmed the antagonistic roles of curcumin to counteract radiation-induced cerebral injury in vivo and suggested that the potent Nrf2 activation capability might be valuable for the protective effects of curcumin against radiation. This provides a potential useful radioprotection dietary component for human populations.

62 citations

Journal ArticleDOI
TL;DR: How aberrant splicing isoforms precisely regulate three basic functional aspects in cancer: proliferation, metastasis and apoptosis is discussed.
Abstract: Pre-mRNA splicing is a fundamental process that plays a considerable role in generating protein diversity. Pre-mRNA splicing is also the key to the pathology of numerous diseases, especially cancers. In this review, we discuss how aberrant splicing isoforms precisely regulate three basic functional aspects in cancer: proliferation, metastasis and apoptosis. Importantly, clinical function of aberrant splicing isoforms is also discussed, in particular concerning drug resistance and radiosensitivity. Furthermore, this review discusses emerging strategies how to modulate pathologic aberrant splicing isoforms, which are attractive, novel therapeutic agents in cancer. Last we outline current and future directions of isoforms diagnostic methodologies reported so far in cancer. Thus, it is highlighting significance of aberrant splicing isoforms as markers for cancer and as targets for cancer therapy.

61 citations


Cited by
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01 Jan 1999
TL;DR: Caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases as discussed by the authors, and they play critical roles in initiation and execution of this process.
Abstract: ■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

2,685 citations

Journal ArticleDOI
TL;DR: The physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes, and sensors, and examples of mitochondrial targeting of bioactive compounds are described.
Abstract: Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, the most effective way to deliver drugs specifically to mitochondria is by covalent linking a lipophilic cation such as an alkyltriphenylphosphonium moiety to a pharmacophore of interest. Other delocalized lipophilic cations, such as rhodamine, natural and synthetic mitochondria-targeting peptides, and nanoparticle vehicles, have also been used for mitochondrial delivery of small molecules. Depending on the approach used, and the cell and mitochondrial membrane potentials, more than 1000-fold higher mitochondrial concentration can be achieved. Mitochondrial targeting has been developed to study mitochondrial physiology and dysfunction and the interaction between mitochondria and other subcellular organelles and for treatment of a variety of diseases such as neurodegeneration and cancer. In this Review, we discuss efforts to target small-molecule compounds to mitochondria for probing mitochondria function, as diagnostic tools and potential therapeutics. We describe the physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes, and sensors, and examples of mitochondrial targeting of bioactive compounds. Finally, we review published attempts to apply mitochondria-targeted agents for the treatment of cancer and neurodegenerative diseases.

892 citations

01 Jan 2009
TL;DR: In this article, a review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
Abstract: MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

646 citations

Journal Article
TL;DR: Mitochondrial dysfunction in response to Ang II modulates endothelial NO˙ and &OV0151; generation, which in turn has ramifications for development of endothelial dysfunction.
Abstract: Mitochondrial dysfunction is a prominent feature of most cardiovascular diseases. Angiotensin (Ang) II is an important stimulus for atherogenesis and hypertension; however, its effects on mitochondrial function remain unknown. We hypothesized that Ang II could induce mitochondrial oxidative damage that in turn might decrease endothelial nitric oxide (NO˙) bioavailability and promote vascular oxidative stress. The effect of Ang II on mitochondrial ROS, mitochondrial respiration, membrane potential, glutathione, and endothelial NO˙ was studied in isolated mitochondria and intact bovine aortic endothelial cells using electron spin resonance, dihydroethidium high-performance liquid chromatography –based assay, Amplex Red and cationic dye fluorescence. Ang II significantly increased mitochondrial H2O2 production. This increase was blocked by preincubation of intact cells with apocynin (NADPH oxidase inhibitor), uric acid (scavenger of peroxynitrite), chelerythrine (protein kinase C inhibitor), NG-nitro-l-arginine methyl ester (nitric oxide synthase inhibitor), 5-hydroxydecanoate (mitochondrial ATP-sensitive potassium channels inhibitor), or glibenclamide. Depletion of p22phox subunit of NADPH oxidase with small interfering RNA also inhibited Ang II–mediated mitochondrial ROS production. Ang II depleted mitochondrial glutathione, increased state 4 and decreased state 3 respirations, and diminished mitochondrial respiratory control ratio. These responses were attenuated by apocynin, 5-hydroxydecanoate, and glibenclamide. In addition, 5-hydroxydecanoate prevented the Ang II–induced decrease in endothelial NO˙ and mitochondrial membrane potential. Therefore, Ang II induces mitochondrial dysfunction via a protein kinase C–dependent pathway by activating the endothelial cell NADPH oxidase and formation of peroxynitrite. Furthermore, mitochondrial dysfunction in response to Ang II modulates endothelial NO˙ and &OV0151; generation, which in turn has ramifications for development of endothelial dysfunction.

579 citations