• Biomolecules & Therapeutics
• /
• 제28권3호
• /
• pp.240-249
• /
• 2020

Despite the therapeutic effect of mesenchymal stem cells (MSCs) in ischemic diseases, pathophysiological conditions, including hypoxia, limited nutrient availability, and oxidative stress restrict their potential. To address this issue, we investigated the effect of melatonin on the bioactivities of MSCs. Treatment of MSCs with melatonin increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). Melatonin treatment enhanced mitochondrial oxidative phosphorylation in MSCs in a PGC-1α-dependent manner. Melatonin-mediated PGC-1α expression enhanced the proliferative potential of MSCs through regulation of cell cycle-associated protein activity. In addition, melatonin promoted the angiogenic ability of MSCs, including migration and invasion abilities and secretion of angiogenic cytokines by increasing PGC-1α expression. In a murine hindlimb ischemia model, the survival of transplanted melatonin-treated MSCs was significantly increased in the ischemic tissues, resulting in improvement of functional recovery, such as blood perfusion, limb salvage, neovascularization, and protection against necrosis and fibrosis. These findings indicate that the therapeutic effect of melatonin-treated MSCs in ischemic diseases is mediated via regulation of PGC-1α level. This study suggests that melatonin-induced PGC-1α might serve as a novel target for MSC-based therapy of ischemic diseases, and melatonin-treated MSCs could be used as an effective cell-based therapeutic option for patients with ischemic diseases.

• International Journal of Oral Biology
• /
• 제44권2호
• /
• pp.50-54
• /
• 2019

Melatonin is a neurotransmitter that modulates various physiological phenomena including regulation and maintenance of the circadian rhythm. Nicotinic acetylcholine receptors (nAChRs) play an important role in oral functions including orofacial muscle contraction, salivary secretion, and tooth development. However, knowledge regarding physiological crosstalk between melatonin and nAChRs is limited. In the present study, the melatonin-mediated modulation of nAChR functions using bovine adrenal chromaffin cells, a representative model for the study of nAChRs, was investigated. Melatonin inhibited the nicotinic agonist dimethylphenylpiperazinium (DMPP) iodide-induced cytosolic free $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) increase and norepinephrine secretion in a concentration-dependent manner. The inhibitory effect of melatonin on the DMPP-induced $[Ca^{2+}]_i$ increase was observed when the melatonin treatment was performed simultaneously with DMPP. The results indicate that melatonin inhibits nAChR functions in both peripheral and central nervous systems.

• Asian-Australasian Journal of Animal Sciences
• /
• 제16권12호
• /
• pp.1701-1704
• /
• 2003

Melatonin regulates circadian rhythms and reproduction changes in seasonally reproductive mammals through binding to high-affinity, G-protein-coupled receptors. Small Tail Han sheep that has significant characteristics of high prolificacy and nonseasonal ovulatory activity is an excellent local sheep breed in P. R. China. The exon 2 of the ovine melatonin receptor 1a (MTNR1A) gene was amplified and a uniform fragment of 824 bp was obtained in 150 ewes of Small Tail Han sheep. The 824 bp PCR product was digested with restriction endonucleases Mnl I and Rsa I, and genetic polymorphism was detected by PCR-RFLP. Polymorphic Mnl I site was detected at base position 605 of the exon 2 of the MTNR1A gene. There were two kinds of genotypes in Small Tail Han sheep, AB (303 bp, 236 bp/67 bp) and BB (236 bp/67 bp, 236 bp/67 bp). The results indicated that genotype AA (303 bp, 303 bp) at Mnl I-RFLP site did not exist in non-seasonal estrous Small Tail Han sheep, which suggested that there was an association between genotype AA (303 bp, 303 bp) and reproductive seasonality in sheep. Polymorphic Rsa I site was detected at base position 604 of the exon 2 of the MTNR1A gene. Three kinds of genotypes were found in Small Tail Han sheep, AA (290 bp, 290 bp), AB (290 bp, 267 bp/23 bp) and BB (267 bp/23 bp, 267 bp/23 bp). Least squares means of litter size in the first parity and the second parity for genotype AA (290 bp, 290 bp) at Rsa I-RFLP site were 0.43 and 1.06 more than those for genotype AB (290 bp, 267 bp/23 bp) in Small Tail Han sheep.

• Asian-Australasian Journal of Animal Sciences
• /
• 제23권10호
• /
• pp.1291-1298
• /
• 2010

The aim of this research was to investigate the dynamic changes of the level of total prolactin receptor (PRLR) mRNA and the short form prolactin receptor (S-PRLR) mRNA in skin of cashmere goats from the initiation of cashmere fibre growth to active growth. Eighteen half-sib wethers were allocated randomly to two groups. Melatonin implants were used in order to initiate growth of cashmere fibre before the normal time and reduce blood plasma prolactin (PRL) concentration. Real-time reverse transcription quantitative polymerase chain reaction (real-time PCR) was used to determine PRLR mRNA expression levels of skin from June to November. The results showed that, in Chinese Inner Mongolia cashmere goats, there were seasonal variations in expression of total PRLR mRNA in skin with levels decreasing from June to October. Synchronously, the cashmere fibre growth rate gradually increased during this period, but the expression levels of S-PRLR mRNA did not decrease along with seasonal variation from initiation to active growth of cashmere fibre. These results suggest that expression levels of S- PRLR mRNA might be involved in the process of cashmere growth. It was also possible that the change of alternative splicing of PRLR occurred in the skin of cashmere goats from proanagen to anagen.

• 한국동물학회:학술대회논문집
• /
• 한국동물학회 1997년도 한국생물과학협회 학술발표대회
• /
• pp.216.1-216
• /
• 1997

No Abstract, See Full Text

• Biomolecules & Therapeutics
• /
• 제24권2호
• /
• pp.115-122
• /
• 2016

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.

• Asian-Australasian Journal of Animal Sciences
• /
• 제19권8호
• /
• pp.1079-1084
• /
• 2006

To determine whether a link exists between reproductive seasonality and the structure of the melatonin receptor 1A (MTNR1A) gene, the latter was studied in nonseasonal estrous breeds (Small Tail Han and Hu ewes) and seasonal estrous breeds (Dorset, Suffolk and German Mutton Merino ewes). A large fragment of the exon 2 of the MTNR1A gene was amplified and a uniform fragment of 824 bp was obtained in 239 ewes of five breeds. The 824 bp PCR product was digested with restriction endonucleases Mnl I and Rsa I, and checked for the presence of restriction sites. The presence (allele M) or absence (allele m) of an Mnl I site at base position 605 led to three genotypes MM (236 bp/236 bp), Mm (236 bp/303 bp) and mm (303 bp/303 bp) in five sheep breeds. The presence (allele R) or absence (allele r) of a Rsa I site at base position 604 led to three genotypes RR (267 bp/267 bp), Rr (267 bp/290 bp) and rr (290 bp/290 bp) in five sheep breeds. Frequencies of MM and RR genotypes were obviously higher, and frequencies of mm and rr genotypes were obviously lower in nonseasonal estrous sheep breeds than in seasonal estrous sheep breeds. Sequencing revealed four mutations (G453T, G612A, G706A, C891T) in mm genotype compared to MM genotype and one mutation (C606T) in rr genotype compared to RR genotype. For polymorphic Mnl I and Rsa I cleavage sites, the differences of genotype distributions were very highly significant (p<0.01) between Small Tail Han ewes and seasonal estrous sheep breeds. In each group, no significant difference (p>0.05) was detected. These results preliminarily showed an association between MM, RR genotypes and nonseasonal estrus in ewes and an association between mm, rr genotypes and seasonal estrus in ewes.

• 한국발생생물학회지:발생과생식
• /
• 제5권1호
• /
• pp.1-8
• /
• 2001

골든 햄스터의 생식활동은 광주기(하루 중 조명 시간)에 의해 결정된다. 광주기는 일년 동안 예측할 수 있는 환경요인이다. 주간 길이가 야간 길이보다 긴 여름에 햄스터의 생식 활동은 왕성하다. 생식 기능을 유지시키는 조명 시간은 하루에 적어도 12.5시간이다. 송과선을 제거시키면 광주기의 정보가 억제되기 때문에, 광주기의 정보는 송과선을 통하여 중재된다. 송과선을 제거 당한 핼스터는 생식 활동이 유지되고, 생식소 기능을 억제하는 상황에서도 생식 기능을 촉진시킨다. 송과선은 멜라토닌을 분비하고 멜라토닌은 광주기 정보를 반영 한다. 멜라토닌을 적절히 투입하면 송과선과 무관하게 생식소 퇴화가 유도된다. 생식체계를 기능적으로 통합하는 신경내분비 신호로 환경 정보가 전환하는 기전을 멜라토닌이 조절함을 시사한다. 광범위한 연구에도 불구하고, 멜라토닌의 작용부위는 알려지지 않았다. 이는 멜라토닌이 생식 호르몬의 분비에 미치는 즉각적인 효과가 없기 때문이다. 그러나, 성적으로 퇴화된 동물들은 생식 호르몬 수준이 낮고 시상하부 내 GnRH 양이 증가한다. 광주기 혹은 멜라토닌 처리가 생식 기능을 억제하는 효과는 GnRH 신경계에 의해 중재됨을 의미한다. 멜라토닌이 GnRH 신경에 미치는 작용 기전이 조사되어야 한다. 멜라토닌 수용체가 클로닝되어, 목적 조직에 미치는 멜라토닌의 작용 기전과 해부학적 위치를 통하여 멜라토닌의 다양하고 잠재적인 능력을 분자수준에서 연구하는데 공헌할 것이다.

• 한국동물학회지
• /
• 제39권4호
• /
• pp.337-351
• /
• 1996

멜라토닌은 대뇌와 소뇌 사이에 위치한 송과선에서 분비되는 호르몬으로 빛이 없는 밤에만 분비된다. 멜라토닌은 분자적 수준에서부터 개체의 행동에 이르기 까지 다양한 기능을 보인다. 특히, 생식에 미치는 영향은 광범위하여, 온대지방에 사는 대부분의 동물은 주위 환경에 적응하여 종족을 유지하는 유일한 계절적 번식을 한다. 햄스터의 생식활동은 여름에 왕성하고 겨울에 정지된다.이는 많은 환경요소중 광주기의 효과가 송과선에 의해 제거하면 광주기의 영향은 사라진다. 즉 생식에 미치는 광주기의 효과가 송과선에 의해 중재 됨을 의미한다. 또한 송과선 호르몬인 멜라토닌의 적절한 처리는 생식활동을 억제한다. 따라서 멜라토닌은 생식에 미치는 광주기의 정보를 생식내분비계로 전달하는 신경전달물질로 사료된다. 시상하부의 특정부위를 절제한 후 광주기나 멜라토닌을 처리하여 멜라토닌의 작용부위에 관한 연구가 되었으나 동물마다 차이점을 보인다. 대부부의 동물에서 공통적인 부위는 suprachiasmatic nuclei와 pars tuberalis이다. 멜라토닌이 생식에 미치는 작용기작은 아직 밝혀지지 않았다. 이는 멜라토닌의 지속적 처리가 멜라토닌의 장기적처리는 이들 호르몬의 분비를 저하시키고, 시상하부에서의 gonadotropin-releasing hormone (GnRH)양을 증가시킨다. 이 결과는 멜라토닌의 지속적인 처리가 시상하부로부터의 GnRH 양을 분비를 감소킴으로써 생식활동을 억제하는 것으로 사료된다.그러나, 멜라토닌에서 GnRH 신경까지의 정보전달은 아직 밝혀지지 않았다. Opioid 신경에 대한 광주기와 멜라토닌의 효과가 동일한 점은 opioid신경의 매개체 역할을 제시하고 있다. 최근에 멜라토닌 수용체가 개구리의 피부와 몇몇 동물의 뇌와 시세포에서 크로닝되었다. 이수용체는 G protein과 관련되고 cAMP 생성을 억제한다. 앞으로 이 멜라토닌 수용체의 존재여부와 분자생물학적 연구는 멜라토닌의 작용부위와 표적세포에서의 작용기작을 설명하는 데 크게 기여할 것으로 기대된다.

• 환경생물
• /
• 제20권3호
• /
• pp.224-231
• /
• 2002

광주기(하루 중 빛의 길이)는 골든 햄스터의 생식을 조절하는 주된 요인이다. 광주기 정보는 멜라토닌을 통하여 생식 내분비계로 전달된다. 따라서 멜라토닌이 생식에 미치는 효과를 여러 광주기에 노출시킨 햄스터에서 조사하였다. 단주기(하루 중 12시간 이하의 조명)에 노출시킨 동물들과 저녁에 멜라토닌을 주사한 동물들의 정소 무게는 현저하게 줄어들었으나, 장주기 (하루 중 12.5시간 이상의 조명)에 유지된 동물과 오전에 멜라토닌을 투여한 동물들의 정소 무게는 줄어들지 않았다. 퇴화된 정소를 조직학적으로 조사한 결과, 세정관 직경이 감소되었고, 세정관내 세포수가 두드러지게 줄어들었다. 또한 생식 능력이 퇴화된 동물의 혈중 여포자극호르몬과 황체호르몬의 수준도 생식 능력을 보유하고 있는 동물에 비해 뚜렷하게 감소하였다. 멜라토닌 수용체가 역전사 polymerase chain reaction으로 동정되었고 조직특이성 또한 조사하였다. 동정된 멜라토닌 수용체는 309염기였으며, 시상하부와 뇌하수체를 포함하는 다양한 장기에서 발현되었다. 생식을 조절하는 핵심 물질인 gonadotropin releasing hormone (GnRH) 유전자의 발현 또한 동정되었다. 그러나 멜라토닌 처리와 광주기 처리는 GnRH유전자 발현에 영향을 미치지 않았다. 종합하면, 광주기의 효과는 멜리토닌을 경유하여 발휘되며, 멜라토닌은 GnRH유전자의 발현보다는, 생성된 GnRH의 분비에 영향을 미쳐 생식내분비계에 간접적으로 작용함을 알 수 있었다.