Age-related changes in melatonin synthesis in rat extrapineal tissues

Abstract

Accepted ManuscriptAge-related changes in melatonin synthesis in rat extrapineal tissues M Sanchez-Hidalgo, C Alarcon de la Lastra, MP Carrascosa-Salmoral, MC Naranjo, A Gomez-Corvera, B Caballero, JM Guerrero PII:S0531-5565 (09) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT AbstractIn the search of new therapeutic targets improving the quality of life of elderly, melatonin, "the chemical expression of darkness", seems to play a remarkable role in aging process possibly due to its antioxidant, immunoenhancer and antiaging properties.The present study was designed to elucidate effects of aging in melatonin extrapineal synthesis and investigate evident age-related alterations in the action mechanisms involved. The presence of the two key enzymes involved in melatonin synthesis, arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) was analyzed in thymus, spleen, liver, kidney and heart of 3-and 12 monthold rats using real time PCR as well as its functionality by enzymatic activity assays. In addition, extrapineal melatonin content was measured by a competitive enzyme immunoassay (ELISA). The results of this study reveal that all rat tissues studied including thymus, and for the first time, spleen, liver, kidney and heart have the necessary machinery to synthesize melatonin. Moreover, we report an age-related decline in rat extrapineal melatonin synthesis with a consequent HIOMT functionality decrease in spleen, liver and heart during physiological aging. On the contrary, NAT enzymatic activity maintains unchanged without evident alterations with advancing age.Moreover, diminished melatonin concentrations were measured in these tissues cited above during aging except in the thymus, where, surprisingly, melatonin content, NAT/HIOMT expression, and enzymatic functionality assays revealed no significant alterations with age. As a conclusion, we report evident age-related changes in melatonin synthesis in some rat peripheral organs. We suggest that thymus may develop compensatory mechanisms to counteract the loss of immune activity and consequently, the loss of this potent antioxidant, during physiological aging.

Effects of Melatonin on Nervous System Aging: Neurogenesis and Neurodegeneration

“…Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone and is produced in vertebrates and invertebrates (28) in pineal and rat extrapineal tissues (29). Its secre-tion follows light/dark (30) and seasonal rhythms (31).…”

Efeito protetor da melatonina sobre intoxicações por herbicidas

“…Além da pineal, a MLT também pode ser secretada em menor quantidade pela retina, ossos, pele, intestino, plaquetas, bile (Acuña-Castroviejo et al 2014), timo, baço, coração, mús-culo esquelético, fígado, estômago, intestino, placenta, testículos, ovários, córtex cerebral e corpo estriado (Stefulj et al 2001, Sanchez-Hidalgo et al 2009). A MLT de produção extrapineal tem uma ação parácrina, autócrina e/ou intrá-crina de proteção contra estresse oxidativo (Luchetti et al 2010) e modulação da resposta imunológica (Carrillo-Vico et al 2004).…”

Non-Ultradian Cardiac Rhythms: Circadian Regulation of the Heart

“…Nightly melatonin secretion by the pineal represents another humoral regulatory arm of the circadian system, though extra-pineal contributions to plasma melatonin levels are not fully characterized in mammals (Huether, 1993). Interestingly, recent evidence demonstrates mammalian cardiac tissue possesses active biosynthetic machinery necessary to produce melatonin (Sanchez-Hidalgo et al, 2009), suggesting that extra-pineal melatonin derived from cardiac tissue may act as a local autocrine or paracrine signal. Numerous beneficial cardioprotective effects have been reported for melatonin (Reiter and Tan, 2009).…”