Melatonin suppresses NO‐induced apoptosis via induction of Bcl‐2 expression in PGT‐β immortalized pineal cells

Yoo, Yeong‐Min; Yim, Sung-Vin; Kim, Sung‐Soo; Jang, Hyun Yong; Lea, Ho Zoo; Hwang, Geun-Cheal; Kim, Jong-Woo; Kim, Soon-Ae; Lee, Hee Jae; Kim, Chang‐Ju; Chung, Joo‐Ho; Leem, Kang‐Hyun

doi:10.1034/j.1600-079x.2002.02899.x

Cited by 67 publications

(50 citation statements)

References 34 publications

(55 reference statements)

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“…Our model showed inhibition of caspase-3 activation by melatonin which consequentially also prevented DNA fragmentation. The melatonin-induced anti-apoptotic effects presented here accorded with results of other studies showing that melatonin inhibits apoptosis in ischemic kidney (Kunduzova et al, 2003) and in amyloid β-peptide injury in hippocampal neurons (Shen et al, 2002) and NO-induced cell death in PGT-β (a cell line of pineal gland tumor) immortalized pineal cells (Yoo et al, 2002). It is interesting that melatonin is not protective in all models of apoptotic cell death (Harms et al, 2000), which may be explained by the fact that not all the investigated noxious stimuli trigger mtPTP-mediated apoptotic pathways.…”

Section: Discussionsupporting

confidence: 78%

Inhibition of mitochondria responsible for the anti-apoptotic effects of melatonin during ischemia-reperfusion

Han

Zhang

Wang

et al. 2006

J. Zhejiang Univ. - Sci. B

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Abstract:Objective: To investigate a possible mechanism responsible for anti-apoptotic effects of melatonin and provide theoretical evidences for clinical therapy. Methods: Ischemia-reperfusion mediated neuronal cell injury model was constructed in cerebellar granule neurons (CGNs) by deprivation of glucose, serum and oxygen in media. After ischemia, melatonin was added to the test groups to reach differential concentration during reperfusion. DNA fragmentation, mitochondrial transmembrane potential, mitochondrial cytochrome c release and caspase-3 activity were observed after subjecting cerebellar granule neurons to oxygen-glucose deprivation (OGD). Results: The results showed that OGD induced typical cell apoptosis change, DNA ladder and apoptosis-related alterations in mitochondrial functions including depression of mitochondrial transmembrane potential (its maximal protection ratio was 73.26%) and release of cytochrome c (its maximal inhibition ratio was 42.52%) and the subsequent activation of caspase-3 (its maximal protection ratio was 59.32%) in cytoplasm. Melatonin reduced DNA damage and inhibited release of mitochondrial cytochrome c and activation of caspase-3. Melatonin can strongly prevent the OGD-induced loss of the mitochondria membrane potential. Conclusion: Our findings suggested that the direct inhibition of mitochondrial pathway might essentially contribute to its anti-apoptotic effects in neuronal ischemia-reperfusion.

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Section: Discussionsupporting

confidence: 78%

Inhibition of mitochondria responsible for the anti-apoptotic effects of melatonin during ischemia-reperfusion

Han

Zhang

Wang

et al. 2006

J. Zhejiang Univ. - Sci. B

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“…This decrease in activation of caspase-3 could be explained by upregulation of Bcl-2 by melatonin. It has been also shown that melatonin suppresses caspase-3 activity via Bcl-2 induction in several cell types (Yoo et al, 2002;Baydas et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

The effects of topical melatonin on oxidative stress, apoptosis signals,and p53 protein expression during cutaneous wound healing

Şener¹,

Çevik²,

Doğan³

et al. 2015

Turk J Biol

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IntroductionWound healing is a complex and well-designed repair process that occurs after any injury, such as surgical procedures or trauma. The process is divided into three serial phases: inflammation, tissue formation, and tissue remodeling (Wu and Chen, 2014). Apoptosis is important to the wound healing process, especially in removing inflammatory cells and inhibiting scar formation. The early phase of inflammation is characterized by the invasion of neutrophils, macrophages, and lymphocytes to the wound area. The fibroblasts then migrate and synthesize extracellular matrix components. Inflammatory cells must be removed in order to begin this next phase of wound healing. Remodeling of granulation tissue during the wound healing process is also accompanied by the apoptosis of fibroblasts (Rai et al., 2005;Wu and Chen, 2014). Dysregulation in these apoptotic processes may result in abnormal wound healing, such as hypertrophic scars and keloid formation (Greenhalgh, 1998), or may delay wound healing (Deveci et al., 2005;Blakytny and Jude, 2006). p53 is generally known as a tumor suppressor and can induce apoptosis via transcription-dependent or -independent mechanisms (Lippens et al., 2009). Reactive oxygen species (ROS) that arise after cutaneous injury may worsen the healing process and induce apoptosis (Hameedaldeen et al., 2014). Low and normal levels of ROS play important roles in wound repair and signal transduction for reepithelialization and proliferation of cells, such as the collagenase activity and the epidermal growth factor signaling. However, higher levels of ROS can cause oxidative stress and may damage intracellular macromolecules such as DNA, lipids, and proteins. Therefore, regulating oxidative stress and the inflammatory response is important during the cutaneous wound healing process (Schäfer and Werner, 2008;Hameedaldeen et al., 2014). The utilization of antioxidants has been considered as an effective therapeutic approach in wound healing (James et al., 2001;Sharifi et al., 2012). Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced primarily by the pineal gland and secreted in the dark during night. It modulates sleep, reproduction, circadian rhythm, and immunity. Additionally, melatonin is a potent antioxidant and directly detoxifies oxygen and nitrogen-based reactants Sener et al., 2009). It affects the activity and the levels of cellular mRNA of antioxidant enzymes including Abstract: Elimination of reactive oxygen species (ROS) can be an important strategy to improve healing of wounds. ROS have an effect on proliferation and cell survival signaling, which results in alteration of apoptotic pathways in cells. Melatonin has antioxidant properties on skin wounds. In our study, we investigated the effects of topical melatonin (3%, w/w) on apoptosis and p53 protein expression together with parameters of oxidative stress in a cutaneous excision wound model. Bcl-2 protein levels in wound tissue at the end of days 3, 7, and 14 were significantly increased, while caspase-3 activity an...

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“…These include downregulation of Bax, caspases, and inhibition of mitochondrial DNA fragmentation, apoptosis, cytochrome c release, and closure of the permeability transition pore. Depression of these adverse events is accompanied by induction of Bcl-2 and improved function of the respiratory chain and ATP synthesis [120][121][122]. Maintenance of mitochondrial glutathione levels has been also attributed to melatonin [94,123].…”

Section: Melatonin and Mitochondriamentioning

confidence: 98%

Melatonin, Oxidative Stress, and the Aging Brain

Bondy

Sharman

2010

Aging and Age-Related Disorders

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The changes associated with brain aging are discussed with emphasis on altered oxidative and inflammatory events and on mitochondrial dysfunction. Many of these changes are exacerbated in a variety of age-related neurologic diseases. This commonality has led to the idea that similar therapeutic approaches may be used in the treatment of several apparently unrelated neurodegenerative disorders. When aspects of these diseases are modeled in experimental animals and cell lines, the application of melatonin has been reported to be advantageous. The means by which melatonin can be protective probably is mediated by way of activation of melatonin receptors, of which several subtypes can be identified. This can initiate a sequence of intracellular signaling events and by activation of transcription factors lead to altered gene expression. The culmination of this cascade can lead to increased levels of antioxidant enzymes and depressed levels of inflammation. Melatonin may be useful both in the retardation of nonpathologic brain aging and in the amelioration of chronic brain disease associated with aging. The inexpensive nature and ready availability of melatonin together with its very low toxicity reinforce the need to place the beneficial properties of this agent on a firmer basis.

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Melatonin suppresses NO‐induced apoptosis via induction of Bcl‐2 expression in PGT‐β immortalized pineal cells

Cited by 67 publications

References 34 publications

Inhibition of mitochondria responsible for the anti-apoptotic effects of melatonin during ischemia-reperfusion

Inhibition of mitochondria responsible for the anti-apoptotic effects of melatonin during ischemia-reperfusion

The effects of topical melatonin on oxidative stress, apoptosis signals,and p53 protein expression during cutaneous wound healing

Melatonin, Oxidative Stress, and the Aging Brain

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