Energy metabolism of normal and lonidamine-treated sertoli cells of rats

Floridi, Aristide; Marcante, Maria Luisa; D’Atri, Stefania; Feriozzi, R.; Menichini, R.; Citro, Gennaro; Cioli, V.; Martino, C. De

doi:10.1016/0014-4800(83)90105-3

Cited by 13 publications

(8 citation statements)

References 21 publications

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“…We found that Sertoli cells produce the high ATP level, which corresponds to the functions of these cells. This result is also in agreement with previous observations that an active energy metabolism occurs within Sertoli cells (Floridi et al 1983, Ueno & Mori 1990.…”

Section: Discussionsupporting

confidence: 93%

Apoptotic spermatogenic cells can be energy sources for Sertoli cells

Xiong¹,

Wang²,

Wu³

et al. 2009

Reproduction

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Apoptotic spermatogenic cells and residual bodies are phagocytosed and degraded by Sertoli cells during mammalian spermatogenesis. The meaning of this event remains to be clarified. In this report, we demonstrate that apoptotic spermatogenic cells and residual bodies can be used to produce ATP by Sertoli cells after phagocytosis of them. Sertoli cells produced the highest level of ATP compared with other testicular cells. Phagocytosis assay in vitro showed that engulfment of apoptotic spermatogenic cells increases ATP production by Sertoli cells. The increased ATP production was detected in seminiferous tubules at the stages where phagocytosis occurs. Induced apoptosis of spermatogenic cells in vivo increased ATP production in seminiferous tubules. The augmentation of ATP production both in vitro and in vivo associated with the lipid formation in Sertoli cells after phagocytosis of apoptotic spermatogenic cells. The lipid b-oxidation was a predominant pathway to produce ATP in Sertoli cells. We conclude that after phagocytosis by Sertoli cells, apoptotic spermatogenic cells are degraded to form lipids that are then used to produce ATP. The results suggest that apoptotic spermatogenic cells can be energy sources for Sertoli cells that may define a novel meaning of spermatogenic cell death.

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Section: Discussionsupporting

confidence: 93%

Apoptotic spermatogenic cells can be energy sources for Sertoli cells

Xiong¹,

Wang²,

Wu³

et al. 2009

Reproduction

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“…They attributed the selective inhibition of glycolysis in tumour cells by LND to its inhibition of mitochondria-bound hexokinase 2 that Pedersen et al [39] had shown was strongly expressed in many tumour cells. However, subsequent studies demonstrated that LND directly inhibited the uncoupled respiration of mitochondria from Ehrlich ascites fueled by various NAD- and FAD-linked substrates but not duroquinol, that feeds electrons directly into complex 3, or ascorbate + N,N,N’,N’-tetramethyl- p -phenylenediamine (TMPD) that feeds electrons into complex 4 via cytochrome c [22;40]. The authors concluded that LND inhibits succinate oxidation within complex 2 of the respiratory chain, which our subsequent studies confirmed [28], while oxidation of pyruvate + malate and other NAD-linked substrates involved a decrease in mitochondrial NADH generation, which might indicate inhibition of dehydrogenases activity.…”

Section: Discussionmentioning

confidence: 99%

The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters

Nancolas

Guo

Zhou

et al. 2016

Biochemical Journal

106

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Lonidamine (LND) is an anti-tumour drug particularly effective at selectively sensitising tumours to chemotherapy, hyperthermia and radiotherapy, although its precise mode of action remains unclear. It has been reported to perturb the bioenergetics of cells by inhibiting glycolysis and mitochondrial respiration, while indirect evidence suggests it may also inhibit L-lactic acid efflux from cells mediated by members of the proton-linked monocarboxylate transporter (MCT) family and also pyruvate uptake into the mitochondria by the mitochondrial pyruvate carrier (MPC). Here we test these possibilities directly. We demonstrate that LND potently inhibits MPC activity in isolated rat liver mitochondria (Ki 2.5 μM) and cooperatively inhibits L-lactate transport by MCT1, MCT2 and MCT4 expressed in Xenopus laevis oocytes with K0.5 and Hill Coefficient values of 36–40 μM and 1.65–1.85. In rat heart mitochondria LND inhibited the MPC with similar potency and uncoupled oxidation of pyruvate was inhibited more effectively (IC50 ~7 μM) than other substrates including glutamate (IC50 ~20 μM). In isolated DB-1 melanoma cells 1–10 μM LND increased L-lactate output, consistent with MPC inhibition, but higher concentrations (150 μM) decreased L-lactate output while increasing intracellular [L-lactate] > five-fold, consistent with MCT inhibition. We conclude that MPC inhibition is the most sensitive anti-tumour target for LND, with additional inhibitory effects on MCT-mediated L-lactic acid efflux and glutamine/glutamate oxidation. Together these actions can account for published data on the selective tumour effects of LND on L-lactate, intracellular pH (pHi) and ATP levels that can be partially mimicked by the established MPC and MCT inhibitor α-cyano-4-hydroxycinnamate.

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“…Presently, the morphological and histochemical modifications of the plasma membrane seem to be related to the functional impairment of the energy metabolism and be con sidered as secondary lesions linked to the agony period of the cells [Bessis, 1964;De Martino. 1974], On the contrary, in the Sertoli cells Lonidamine induces morphological and functional modifications [De Mar tino el al., 1975Marcante et al, 1981] without affecting their energy metabolism [Floridi et al. 1983].…”

Section: Discussionmentioning

confidence: 99%

“…liver, and tumor cells, as well as the determination of mitochondrially bound hexokinase and the binding of Lonidamine to mitochondria and mitoplasts have been extensively described in previous papers [Floridi et al, 1981a[Floridi et al, , c. d. 1982[Floridi et al, . 1983.…”

Section: Isolated Mitochondriamentioning

confidence: 99%

Effects of Lonidamine on Murine and Human Tumor Cells in vitro

Battelli

Mg³

et al. 1984

Oncology

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Lonidamine induces in murine and human tumor cells severe morphological damage of the mitochondria and other cytoplasmic structures both ‘in vitro’ and ‘in vivo’. Biochemical studies have demonstrated that the drug decreases oxygen consumption and lactate production. The sensitivity of human tumor cells is not related to their histotype. Lonidamine’s effects on mitochondria, glycolysis, pentose phosphate pathway, and aromatase activity are discussed.

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Energy metabolism of normal and lonidamine-treated sertoli cells of rats

Cited by 13 publications

References 21 publications

Apoptotic spermatogenic cells can be energy sources for Sertoli cells

Apoptotic spermatogenic cells can be energy sources for Sertoli cells

The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters

Effects of Lonidamine on Murine and Human Tumor Cells in vitro

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