Zinc deficiency accompanies hypothyroidism in mice altering proliferation and intracellular signaling. Zinc supplementation reverses immunosuppression in hypothyroid mice

PAULAZO MA, ; STERLE H, ; BARREIRO ARCOS ML, ; DIAZ FLAQUE MC,; CAYROL F, ; CREMASCHI GA, ; KLECHA AJ

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

SAIC y SAI

􀀼inc 􀀊􀀼n􀀋 is essential for all highly proliferating cells, especiallythose of the immune system. 􀀼n deficiency 􀀊􀀼n􀀦􀀋 affectsthe functioning of many proteins crucial for intracellular signalsin immunocompetent cells. Furthermore, it is required for optimalactivity of many hormones, including thyroid hormones 􀀊TH􀀋. Also,it 􀁙as demonstrated that hypothyroidism leads to immunosuppression,but alterations of 􀀼n levels 􀁙ere not studied. 􀀱ur aim􀁙as to evaluate the effect of 􀀼n􀀦 on lymphocyte function both invitro and in vivo, and its impact in hypothyroid status. 􀀴eversionof these effects by 􀀼n supplementation 􀁙as studied as 􀁙ell. Forin vitro assays, cells 􀁙ere cultured in the absence or presence ofspecific intra􀀏􀀊T􀀲E􀀰􀀋 or extracellular 􀀊􀀦T􀀲A􀀋 􀀼n chelators. 􀀼n􀀦 invivo 􀁙as evaluated in lymphocytes from mice fed a reduced 􀀼ndiet and hypothyroidism by propylthiouracil treatment. 􀀤oth 􀀼nchelators significantly inhibited proliferative responses of T cells,stimulated 􀁙ith the T cell􀀏mitogen ConA. To ascertain the inductionof apoptosis, caspase􀀏􀀕 activity, cell binding of annexin 􀀸 / propidiumiodide, nuclear condensation and 􀀦􀀰A fragmentation 􀁙ereevaluated. 􀀫n all cases, a remar􀁍able induction of apoptosis 􀁙asobserved in cells treated 􀁙ith chelators 􀀊p􀀞􀀒.􀀒􀀗􀀋. Also, 􀀼n chelatorsinhibited E􀀴􀀭 phosphorylation induced 􀁙ith ConA 􀀊p􀀞􀀒.􀀒􀀗􀀋.All these effects 􀁙ere reverted 􀁙ith the addition of 􀀼n 􀀊p􀀞􀀒.􀀒􀀓􀀋.Similar effects 􀁙ere observed on T cells from 􀀼n􀀦 mice. Hypothyroidmice sho􀁙ed decreased T lymphocyte activity, together􀁙ith lo􀁙 levels of circulating TH and decreased lymph node andfemur 􀀼n levels. 􀀼n supplementation 􀁙as not able to reverse thehormonal levels, although it reversed T cell function impairment.􀀱ur results sho􀁙ed that 􀀼n􀀦 lead to altered lymphoid intracellu larsignaling thus affecting cell proliferation and contributing to theimmunosuppression of hypothyroid conditions. 􀀼n supplementation􀁙ould be a complementary treatment for hypothyroid patients.