Heavy metals, such as lead (Pb2+), are usually accumulated in human bodies and impair human's health. Lead is a metal with many recognized adverse health side effects and yet the molecular processes underlying lead toxicity are still poorly understood. In the present study, we proposed to investigate the effects of lead toxicity in cultured cardiofibroblasts. After lead treatment, cultured cardiofibroblasts showed severe endoplasmic reticulum (ER) stress. However, the lead-treated cardiofibroblasts were not dramatically apoptotic. Further, we found that these cells determined to undergo autophagy through inhibiting mammalian target of rapamycin complex 1 (mTORC1) pathway. Moreover, inhibition of autophagy by 3-methyladenine (3-MA) may dramatically enhance lead toxicity in cardiofibroblasts and cause cell death. Our data establish that lead toxicity induces cell stress in cardiofibroblasts and protective autophagy is activated by inhibition of mTORC1 pathway. These findings describe a mechanism by which lead toxicity may promote the autophagy of cardiofibroblasts cells, which protects cells from cell stress. Our findings provide evidence that autophagy may help cells to survive under ER stress conditions in cardiofibroblasts and may set up an effective therapeutic strategy for heavy metal toxicity.

Based on the complex ligand NiL (H 2 L = 3,12-dichloro-8-methyl-5-phenyl-5,6,7,8,9,10,15,18-octahydro-6,9,15,18-tetraaza-dibenzocyclotetradecene-16,17-dione), a dinuclear complex [(NiL)Cu-(phen)(EtOH)](ClO 4 ) 2 ·EtOH·0.5H 2 O (1) and two tetranuclear com-

Two new oxamido‐bridged N4 macrocyclic complexes [(CuL)2Mn(C2H5OH)2](ClO4)2·2C2H5OH (1) and [(CuL)2Co‐(C2H5OH)2](ClO4)2·2C2H5OH (2) (H2L = 2,3‐dioxo‐5,6:14,15‐di‐benzo‐7,13‐diphenyl‐1,4,8,12‐tetraazacyclo‐pentadeca‐7,13‐diene) have been synthesized and structurally characterized by X‐ray crystallographic investigations. In the two complexes, all copper(II) ions adopt a slightly distorted square‐planar configuration and the central manganese(II) and cobalt(II) ions are set in a distorted octahedral coordination sphere, connected to the other CuL fragments through exo‐cis oxamido bridges. The analyses of the magnetic properties were carried out by means of the theoretical expression of the magnetic susceptibility deduced from the spin Hamiltonian Ĥ = –2JŜ1Ŝ2, leading to J = –14.58 cm–1 for complex 1 and J = –26.95 cm–1 for complex 2, respectively.

A new oxamido‐bridged macrocyclic trinuclear complex {[(CuL)(EtOH)]2Cd(EtOH)2}(ClO4)2·H2O (H2L = 2,3‐dioxo‐5,6:13,14‐dichlorobenzo‐7,12‐diphenyl‐1,4,8,11‐tetraazacyclo‐pentadeca‐7,11‐diene)was synthesized and structurally characterized. The central CdII ion of the complex is bridged by macrocyclic oxamido groups. Magnetic properties were studied by susceptibility vs. temperature measurement, the best fitting of the experimental data led to J = –0.59 cm–1. IR and EPR spectra were also investigated.