Humanin delays apoptosis in K562 cells by downregulation of P38 MAP kinase

Wang, Dongmei; Li, H.; Hu, Yuan; Zheng, Mingqi; Bai, Chujie; Chen, L.; Pei, Xin-Yan

doi:10.1007/s10495-005-1191-x

Cited by 47 publications

(31 citation statements)

References 34 publications

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“…It has been reported that the neuroprotective effect of humanin against cerebral ischemia/reperfusion injury is mediated by inhibiting ERK activation [42]. Studies have also shown that humanin could protect cultured mouse primary cortical neurons from OGD-induced injury via the PI3K/Akt pathway [43], suppress apoptosis induced by ischemia/reperfusion or other factors by downregulating p38 MAP kinase [40] and interfere with Bax activation [12,22,35], and prolong the survival of serumdeprived human lymphocytes by increasing the metabolic activity of individual lymphocytes [23]. Studies on the mechanisms involved in the neuroprotective effect of humanin against AD-related neurotoxicities have demonstrated that the binding with a novel IL-6-receptor-related receptor(s) involving CNTFRalpha, WSX-1 and gp130 on the cell surface [16,17,28] and the activation of the JAK2/ STAT3 signaling axis [5] are associated with the neuroprotective effect of humanin.…”

Section: Discussionmentioning

confidence: 99%

“…Neuroprotective effect of humanin against cerebral ischemia/reperfusion (I/R) injury in mice has been reported to be mediated at least in part by inhibiting ERK activation [42] and the PI3K/Akt pathway [43]. Humanin could suppress apoptosis, induced by ischemia/reperfusion or other factors, by down-regulating p38 MAP kinase [40,41] and interfering with Bax activation [12,22,25].…”

Section: Introductionmentioning

confidence: 99%

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Humanin Protects Cortical Neurons from Ischemia and Reperfusion Injury by the Increased Activity of Superoxide Dismutase

et al. 2011

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The neuroprotective effects of superoxide dismutase (SOD) against hypoxia/reperfusion (I/R) injury and of humanin (HN) against toxicity by familial amyotrophic lateral sclerosis (ALS)-related mutant SOD led us to hypothesize that HN might have a role to increase the activity of SOD, which might be involved in the protective effects of HN on neuron against Alzheimer's disease-unrelated neurotoxicities. In the present study, we found that 4 h ischemia and 24 h reperfusion induced a significant increase in lactate dehydrogenase (LDH) release, malondialdehyde (MDA) formation and the number of karyopyknotic nuclei (4',6-diamidino-2-phenylindole dihydrochloride nuclear dyeing) and a decrease in the number of Calcein-AM-positive living cells and cell viability. Pretreatment of the cells with HN led to a significant decrease in LDH release, MDA formation and the number of karyopyknotic nuclei, and an increase in the number of Calcein-AM-positive living cells and cell viability in neurons treated with I/R. We also found a significant decrease in SOD activity in neurons treated with I/R only, while pre-treatment with HN before I/R induced a significant increase in the activity of SOD as compared with the I/R group. Our findings implied that HN protects cortical neurons from I/R injury by the increased SOD activity and that the protective effect of HN on neurons against I/R is concentration-dependent.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Humanin Protects Cortical Neurons from Ischemia and Reperfusion Injury by the Increased Activity of Superoxide Dismutase

et al. 2011

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“…Our results showed that treatment with GA resulted in down-regulation of BCL-2, which suggested GA might induce cell apoptosis through suppressing mitochondrial pathways. Traditional clinicopathologic factors and several interesting molecules, including phosphatidylinositol 3-kinase (PI3K) [24], oncogenes such as c-myc [25], and nuclear factor-kappa B (NF-κB) have been reported to correlate to the prognosis of leukemia patients. Previous studies have also revealed numerous cellular proteins (e.g., c-myc, PI3K and AKT) were targeted by GA in several cell lines [2,26,27].…”

Section: Discussionmentioning

confidence: 99%

Anticancer Effect and Apoptosis Induction of Gambogic Acid in Human Leukemia Cell Line K562 In Vitro

Ouyang

2015

Med Sci Monit

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BackgroundThe aim of this study was to investigate the anticancer effect and related mechanisms of gambogic acid (GA), a traditional Chinese medicine, on human leukemia cell line K562, together with the effect on bone marrow mononuclear cells (MNCs).Material/MethodsK562 cells and MNCs were treated with various concentrations and treatment times of GA. Inhibitory rate was detected by use of the Cell Counting Kit-8 (CCK-8) assay. Apoptosis was analyzed by morphological detection, Annexin-V/PI doubling staining, and TUNEL assays. The expression changes of pivotal proteins were evaluated by Western blotting.ResultsGA not only suppressed cell proliferation, but also induced apoptosis of K562 cells in a dose-dependent manner. While it did not significantly inhibit cell proliferation of MNCs, it did induce apoptosis in a dose-dependent manner. CCK-8 assay revealed that the proliferation of K562 cells was significantly inhibited when the concentration of GA was more than 0.5 μM. Morphological detection showed the nuclei became denser and more intense orange in K562 cells after GA treatment compared with the untreated group. The expression levels of BCL-2, nuclear factor-κB (NF-κB), c-myc, phosphatidylinositol3-kinase (PI3K), and phosphorylation of serine-threonine kinase (p-AKT) were down-regulated by GA.ConclusionsGA significantly suppressed the proliferation of K562 cells, but has less effect on MNCs. The inhibition of K562 cells proliferation and apoptosis induced by GA might be related to the down-regulation of BCL-2, NF-κB, c-myc, PI3K, and p-AKT.

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“…ERK and PI3K-Akt pathways are implicated in neuroprotection of HN against cerebral ischemia/reperfusion injury in vivo [25], [26]. p38 and STAT3 are involved in apoptosis induced by trophic factor withdrawal in human leukemia cell line and pancreatic beta-cell line, respectively [28], [70]. In this study, we did not detect significant changes in phosphorylation of Tyr705 in STAT3 and Ser473 in Akt, while phosphorylation of Thr308 in Akt was significantly increased in S14G-HN-treaed 3xTg-AD mouse brains compared with control (Fig.…”

Section: Discussionmentioning

confidence: 99%

A Humanin Derivative Reduces Amyloid Beta Accumulation and Ameliorates Memory Deficit in Triple Transgenic Mice

et al. 2011

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Humanin (HN), a 24-residue peptide, was identified as a novel neuroprotective factor and shows anti-cell death activity against a wide spectrum of Alzheimer's disease (AD)-related cytotoxicities, including exposure to amyloid beta (Abeta), in vitro. We previously demonstrated that the injection of S14G-HN, a highly potent HN derivative, into brain ameliorated memory loss in an Abeta-injection mouse model. To fully understand HN's functions under AD-associated pathological conditions, we examined the effect of S14G-HN on triple transgenic mice harboring APPswe, tauP310L, and PS-1M146V that show the age-dependent development of multiple pathologies relating to AD. After 3 months of intranasal treatment, behavioral analyses showed that S14G-HN ameliorated cognitive impairment in male mice. Moreover, ELISA and immunohistochemical analyses showed that Abeta levels in brains were markedly lower in S14G-HN-treated male and female mice than in vehicle control mice. We also found the expression level of neprilysin, an Abeta degrading enzyme, in the outer molecular layer of hippocampal formation was increased in S14G-HN-treated mouse brains. NEP activity was also elevated by S14G-HN treatment in vitro. These findings suggest that decreased Abeta level in these mice is at least partly attributed to S14G-HN-induced increase of neprilysin level. Although HN was identified as an anti-neuronal death factor, these results indicate that HN may also have a therapeutic effect on amyloid accumulation in AD.

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Humanin delays apoptosis in K562 cells by downregulation of P38 MAP kinase

Cited by 47 publications

References 34 publications

Humanin Protects Cortical Neurons from Ischemia and Reperfusion Injury by the Increased Activity of Superoxide Dismutase

Humanin Protects Cortical Neurons from Ischemia and Reperfusion Injury by the Increased Activity of Superoxide Dismutase

Anticancer Effect and Apoptosis Induction of Gambogic Acid in Human Leukemia Cell Line K562 In Vitro

A Humanin Derivative Reduces Amyloid Beta Accumulation and Ameliorates Memory Deficit in Triple Transgenic Mice

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