Table 2.
Mitochondrial dysfunction pathway in the pathogenesis of pituitary adenomas.
| References | Biological process | The related molecules | Function mechanism | Species |
|---|---|---|---|---|
| An et al. (41) | Energy metabolism | Lactate dehydrogenase A (LDHA) | LDHA suppresses glucose uptake, lactate secretion, invasion and proliferation. | GH3 cells |
| Casar-Borota et al. (42) | Energy metabolism | Isocitrate dehydrogenase (IDH) 1 and 2 | Mutant IDH1 and IDH2. | Human tissue specimen |
| Hao et al. (43) | Energy metabolism | Isocitrate dehydrogenase 1 (IDH1) | Somatic IDH1 mutation. | Human tissue specimen |
| Porcelli et al. (44) | Energy metabolism | Hypoxia inducible factor 1 subunit alpha(HIF1A) | A high frequency of homoplasmic disruptive mutations implicates disassembly of respiratory complex I in vivo which in turn contributes to the inability of oncocytic tumors to stabilize HIF1alpha. | Human tissue specimen and cell |
| Xekouki and Stratakis (45) | Energy metabolism | Succinate dehydrogenase (SDHx) | Loss of heterozygosity at the SDHD locus. | Human tissue specimen |
| Xekouki et al. (46) | Energy metabolism | Succinate dehydrogenase (SDH) | SDHD mutation. | Human tissue specimen and rats |
| Wu et al. (47) | Energy metabolism | Hsa-mir-181a-5p | Prolactin signaling pathway, and mitochondria related calcium reabsorption. | Human tissue specimen |
| Feng et al. (48) | Energy metabolism | 14-3-3η protein | 14-3-3η is exclusively overexpressed in oncocytomas, and 14-3-3η is capable of inhibiting glycolysis, leading to mitochondrial biogenesis in the presence of rotenone. In particular, 14-3-3η inhibits LDHA by direct interaction in the setting of complex I dysfunction. | Human tissue specimen and cell |
| Wang et al. (29) | Oxidative stress | Reactive oxygen species (ROS) and Ca2+ concentration | Activation of ROS/MAPKs-mediated pathway. | MMQ and GH3 cells |
| Pawlikowski et al. (49) | Oxidative stress | Nitric oxide synthase (NOS) | NOS immunoreactivity is also detectable in all but two human pituitary adenomas and seems to negatively correlate with microvascularization. | Human tissue specimen and rats |
| Sabatino et al. (50) | Oxidative stress | Nuclear factor, erythroid 2 like 2 (Nrf2) | The evidence of oxidative stress in pituitary cells, accompanies by bigger and round mitochondria during tumor development, associates with augmented biogenesis and an increased fusion process. | Rats |
| Jaubert et al. (51) | Oxidative stress | Dopamine (DA) | (i) loss of mitochondrial potential; (ii) relocation of Bax to the mitochondria; (iii) cytochrome c release; (iv) caspase-3 activation, and (v) nuclear fragmentation, resulting in apoptosis. | GH3 cells |
| Onishi et al. (52) | Oxidative stress | The inducible NOS (iNOS) | Invasive adenomas have higher iNOS immunoreactivity, and this correlates with the MIB-1 labeling index. | Human tissue specimen |
| Huang et al. (53) | Oxidative stress | Nitric oxide (NO) | Nitric oxide mediates Nivalenol (NIV)-induced oxidative stress. Additionally, NIV induces caspase-dependent apoptosis, decrease in mitochondrial membrane potential and mitochondrial ultrastructural changes. | GH3 cells |
| Babula et al. (54) | Oxidative stress | Nitric oxide (NO) metabolites level in serum | The decrease of NO level after pituitary adenoma resection indicates the relationship between NO synthesis and pituitary adenoma occurrence. | Human |
| Guzzo et al. (55) | Apoptosis | Bcl-2 family | The intrinsic pathway (or mitochondrial) and extrinsic (or death-receptor pathway) | Rat pituitary cell lines, and human pituitaries tissue |
| Gottardo et al. (56) | Apoptosis | Humanin (HN) and Rattin (HNr) | Intratumor injection of BV-shHNr to nude mice bearing s.c. GH3 tumors increases the number of apoptotic cells, delays tumor growth, and enhances survival rate, suggesting that endogenous HNr may be involved in pituitary tumor progression. | GH3 cells |
| Gao et al. (57) | Apoptosis | Trefoil factor 3 (TFF3) | TFF3 protein level in pituitary adenoma is about 3.61 ± 0.48 folds of that in normal tissues (P < 0.01). After transfecting with small interference RNA (siRNA) against TFF3, the apoptotic ration is significantly elevated. | Human pituitary adenoma cell HP75 |
| Tanase et al. (58) | Apoptosis | Apoptotic protease-activating factor-1 (APAF-1) | A bidirectional-inverted relationship between APAF-1 and cathepsin B expressions may result in changes in pituitary adenoma behavior. | Human tissue specimen |
| Yang et al. (59) | Apoptosis | MicroRNA-34a | miR-34a expression is significantly lower in GH4C1 cells, whereas miR-34a overexpression significantly inhibits GH4C1 cell proliferation and promotes cell apoptosis though SRY-box 7 (SOX7). | Rats |
| Cui et al. (60) | Apoptosis | MicroRNA-21 | MiR-21 targets 3'-UTR of PITX2 gene to inhibit its expression. The elevated miR-21 and/or silencing PITX2 significantly depress PITX2 expression in HP75 cells, potentiate caspase-3 activity, decrease cell proliferation, and facilitate apoptosis. | Human tissue specimen |
| Wang et al. (39) | Apoptosis | MicroRNA-200c | MicroRNA-200c expression was inversely associated with Pten expression and facilitated apoptosis. | GH3 cells |
| Gong et al. (61) | Apoptosis | Adrenocorticotrophic hormone | UA inhibits the viability, and induces apoptosis of AtT20 cells, and decreases ACTH secretion. | AtT20 cells |
| Deyu et al. (36) | Autophagy | T-2 toxin | T-2 toxin induces abnormal cell morphology, cytoplasm and nuclear shrinkage, nuclear fragmentation and formation of apoptotic bodies, and autophagosomes. | GH3 cells |
| Kim et al. (37) | Autophagy | Cyclosporine A | Bcl-2 levels showed drug dose-dependent augmentation in autophagy and were decreased in apoptosis. | GH3 cells |
| Leng et al. (38) | Autophagy | Dopamine agonists | The increasing Reactive oxygen species (ROS) inhibited the MTOR pathway, induced macroautophagy/autophagy, and led to autophagic cell death (ACD) in vitro and in vivo. | Human pituitary tumor cell |
| Tagliati et al. (62) | Tumor immune | Presequence translocase associated motor 16 (MAGMAS) | Mitochondria-associated protein is involved in granulocyte-macrophage colony-stimulating factor signal transduction. | Human tissue specimen and AtT-20 D16v-F2 cells |